Asciminib: Drug information

(For additional information see "Asciminib: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: US

Scemblix

Brand Names: Canada

Scemblix

Pharmacologic Category

Antineoplastic Agent, BCR-ABL Tyrosine Kinase Inhibitor;
Antineoplastic Agent, STAMP Inhibitor;
Antineoplastic Agent, Tyrosine Kinase Inhibitor

Dosing: Adult

Chronic myeloid leukemia, Philadelphia chromosome-positive, chronic phase, previously treated with ≥2 tyrosine kinase inhibitors

Chronic myeloid leukemia, Philadelphia chromosome-positive (Ph+), chronic phase, previously treated with ≥2 tyrosine kinase inhibitors: Oral: 80 mg once daily or 40 mg twice daily (Ref) until treatment failure or unacceptable toxicity.

Chronic myeloid leukemia, Philadelphia chromosome-positive, chronic phase, with T315I mutation

Chronic myeloid leukemia, Philadelphia chromosome-positive, chronic phase, with T315I mutation: Oral: 200 mg twice daily until treatment failure or unacceptable toxicity.

Missed dose: If a once-daily dose is missed by more than ~12 hours, skip the dose and administer the next dose as scheduled. If a twice-daily dose is missed by more than ~6 hours, skip the dose and administer the next dose as scheduled.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

eGFR 15 to 89 mL/minute/1.73 m²(not requiring dialysis): No dosage adjustment is necessary.

Patients requiring dialysis: There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

No dosage adjustment is necessary.

Dosing: Adjustment for Toxicity: Adult

**Asciminib Dosage Reduction Levels in Philadelphia Chromosome-Positive (Ph+) Chronic Myeloid Leukemia**
Dose reduction	Dose for Ph+ chronic phase CML^a in patients previously treated with ≥2 tyrosine kinase inhibitors	Dose for Ph+ chronic phase CML with the T315I mutation
^a CML = Chronic myeloid leukemia.
Initial (usual) dose	80 mg once daily or 40 mg twice daily	200 mg twice daily
First dose reduction	40 mg once daily or 20 mg twice daily	160 mg twice daily
Subsequent dose reduction	Permanently discontinue asciminib if unable to tolerate 40 mg once daily or 20 mg twice daily.	Permanently discontinue asciminib if unable to tolerate 160 mg twice daily.

**Asciminib Dosage Modification for Adverse Reactions**
Adverse reaction	Severity	Dosage modification
Hematologic toxicity
Neutropenia and/or thrombocytopenia	ANC <1,000/mm³ and/or platelets <50,000/mm³	Withhold asciminib until ANC is ≥1,000 mm³ and/or platelets are ≥50,000/mm³. If resolved within 2 weeks, resume asciminib at the same (starting) dose. If resolved after >2 weeks, resume asciminib at a reduced dose. For recurrent severe neutropenia and/or thrombocytopenia, withhold asciminib until ANC is ≥1,000 mm³ and/or platelets are ≥50,000/mm³, then resume asciminib at a reduced dose.
Nonhematologic toxicity
Cardiovascular toxicity	Any	Initiate appropriate treatment as clinically indicated.
Cardiovascular toxicity	Grade 3 or higher	Withhold asciminib until recovery to ≤ grade 1, then resume at a reduced dose. If not resolved, permanently discontinue asciminib.
GI (ie, pancreatic) toxicity	Asymptomatic amylase and/or lipase elevation >2 × ULN	Withhold asciminib until resolved to <1.5 × ULN, then resume at a reduced dose. If not resolved, permanently discontinue asciminib and evaluate for pancreatitis. If amylase and/or lipase elevation >2 × ULN recurs (at the reduced dose), permanently discontinue asciminib.
GI (ie, pancreatic) toxicity	Amylase and lipase elevations with concomitant abdominal symptoms	Temporarily withhold asciminib and evaluate as clinically necessary to exclude pancreatitis.
Hypersensitivity reactions	Any	Initiate appropriate treatment as clinically indicated.
Hypersensitivity reactions	Grade 3 or higher	Withhold asciminib until recovery to ≤ grade 1, then resume at a reduced dose. If not resolved, permanently discontinue asciminib.
Hypertension	Any	Monitor and manage with standard antihypertensive therapy as clinically indicated.
Hypertension	Grade 3 or higher	Withhold asciminib until recovery to ≤ grade 1, then resume at a reduced dose. If not resolved, permanently discontinue asciminib.
Other adverse reactions	Grade 3 or higher	Withhold asciminib until recovery to ≤ grade 1, then resume at a reduced dose. If not resolved, permanently discontinue asciminib.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults without the T315I mutation.

>10%:

Cardiovascular: Hypertension (14%), increased serum creatine kinase (30%)

Dermatologic: Skin rash (18%)

Endocrine & metabolic: Decreased serum calcium (corrected: 16%), decreased serum phosphate (18%), decreased serum potassium (11%), increased serum cholesterol (12%), increased serum triglycerides (44%), increased uric acid (21%)

Gastrointestinal: Abdominal pain (14%), diarrhea (13%), increased serum amylase (13%), increased serum lipase (15%), nausea (12%; grades 3/4: <1%)

Hematologic & oncologic: Decreased hemoglobin (37%; grades 3/4: 2%; including anemia), decreased neutrophils (43%; grades 3/4: 22%; including neutropenia), decreased platelet count (46%; grades 3/4: 24%; including thrombocytopenia), lymphocytopenia (20%; grades 3/4: 3%)

Hepatic: Increased serum alanine aminotransferase (26%), increased serum alkaline phosphatase (13%), increased serum aspartate aminotransferase (21%), increased serum bilirubin (12%)

Hypersensitivity: Hypersensitivity reaction

Nervous system: Fatigue (20%), headache (21%)

Neuromuscular & skeletal: Arthralgia (13%), musculoskeletal pain (24%)

Renal: Increased serum creatinine (15%)

Respiratory: Upper respiratory tract infection (26%)

1% to 10%:

Cardiovascular: Cardiac arrhythmia (<10%), edema (<10%), heart failure (<10%), palpitations (<10%), prolonged QT interval on ECG (<10%)

Dermatologic: Pruritus (<10%), urticaria (<10%)

Endocrine & metabolic: Hypothyroidism (<10%)

Gastrointestinal: Constipation (<10%), decreased appetite (<10%), pancreatitis, vomiting (<10%)

Genitourinary: Urinary tract infection (<10%)

Hematologic & oncologic: Febrile neutropenia (<10%), hemorrhage (<10%)

Infection: Influenza (<10%)

Nervous system: Dizziness (<10%), peripheral neuropathy (<10%)

Ophthalmic: Blurred vision (<10%), dry eye syndrome (<10%)

Respiratory: Cough (<10%), dyspnea (<10%), lower respiratory tract infection (<10%), pleural effusion (<10%), pneumonia (<10%)

Miscellaneous: Fever (<10%)

Frequency not defined: Cardiovascular: Cardiovascular toxicity (arterial thromboembolism, cerebral ischemia, ischemic heart disease, thromboembolic disease)

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to asciminib or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Thrombocytopenia, neutropenia, and anemia have occurred with asciminib, including grade 3 and 4 events. The median time to first occurrence of grade 3 or 4 thrombocytopenia, neutropenia, or anemia was 6 weeks (range: 0.1 to 64 weeks), 6 weeks (range: 0.1 to 180 weeks), or 30 weeks (range: 0.4 to 207 weeks), respectively.

• Cardiovascular toxicity: Cardiovascular toxicity, including ischemic cardiac and CNS conditions, arterial thrombotic and embolic conditions, and heart failure, has been reported (including fatalities). Grade 3 and 4 cardiovascular toxicity has occurred, as well as grade 3 cardiac failure. Cardiovascular toxicity occurred in patients with preexisting cardiovascular conditions or risk factors, and/or prior exposure to multiple tyrosine kinase inhibitors. Arrhythmia (including QTc prolongation) has been reported, including grade 3 events.

• GI toxicity: Pancreatitis has been reported with asciminib, including grade 3 pancreatitis in a small number of patients. Asymptomatic lipase and amylase elevations occurred in approximately one-fifth of patients; grade 3 and 4 pancreatic enzyme elevations also were reported.

• Hypersensitivity: Hypersensitivity reactions were reported in almost one-third of patients, including rare grade 3 or 4 events. Reactions included rash, edema, and bronchospasm.

• Hypertension: Hypertension occurred in almost one-fifth of patients receiving asciminib, including grade 3 and 4 hypertension. The median time to first occurrence of grade 3 or 4 hypertension was 14 weeks (range: 0.1 to 156 weeks).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Scemblix: 20 mg, 40 mg

Generic Equivalent Available: US

Pricing: US

Tablets (Scemblix Oral)

20 mg (per each): $434.27

40 mg (per each): $434.27

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.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Scemblix: 20 mg, 40 mg

Administration: Adult

Oral: Administer on an empty stomach; avoid food for at least 2 hours before and 1 hour after asciminib administration. If administering once daily, administer at approximately the same time each day; if administering twice daily, administer approximately every 12 hours. Swallow tablets whole; do not break, crush, or chew.

Hazardous Drugs Handling Considerations

This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Asciminib may cause reproductive toxicity, teratogenicity, and has a structural or toxicity profile similar to existing hazardous agents.

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.

Use: Labeled Indications

Chronic myeloid leukemia, chronic phase: Treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase, in adults previously treated with 2 or more tyrosine kinase inhibitors or with the T315I mutation.

Medication Safety Issues

Sound-alike/look-alike issues:

Asciminib may be confused with abciximab, abemaciclib, afatinib, alectinib, alpelisib, avapritinib, axitinib, bosutinib, dasatinib, imatinib, nilotinib, ponatinib.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of BCRP/ABCG2, CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C8 (weak), CYP2C9 (moderate), CYP3A4 (weak)

Drug Interactions

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

Alitretinoin (Systemic): CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with moderate CYP2C9 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a moderate CYP2C9 inhibitor. Risk D: Consider therapy modification

ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy

Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy

Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Atorvastatin: Asciminib may increase the serum concentration of Atorvastatin. 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

BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors): Asciminib may increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Cannabis: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased. Risk C: Monitor therapy

CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy

Carvedilol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Risk C: Monitor therapy

Celecoxib: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Celecoxib. Risk C: Monitor therapy

Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

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

CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Asciminib. Risk C: Monitor therapy

Daprodustat: CYP2C8 Inhibitors (Weak) may increase the serum concentration of Daprodustat. Risk C: Monitor therapy

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

Diclofenac (Systemic): CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Diclofenac (Systemic). Risk C: Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy

DroNABinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of DroNABinol. Risk C: Monitor therapy

Erdafitinib: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Erdafitinib. Management: Avoid concomitant use of erdafitinib and moderate CYP2C9 inhibitors when possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose modifications accordingly. Risk D: Consider therapy modification

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Etravirine: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Etravirine. Risk C: Monitor therapy

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

Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy

Flurbiprofen (Systemic): CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Flurbiprofen (Systemic). Risk C: Monitor therapy

Fluvastatin: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Fluvastatin. Management: Fluvastatin should be used at the lowest effective dose and should not exceed 20 mg twice daily when combined with moderate CYP2C9 inhibitors. Avoid coadministration of fluvastatin extended-release tablets with moderate CYP2C9 inhibitors. Risk D: Consider therapy modification

Fosphenytoin-Phenytoin: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Imatinib: May increase the serum concentration of Asciminib. Risk C: Monitor therapy

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

Itraconazole: May decrease the serum concentration of Asciminib. Specifically, the hydroxypropyl-beta-cyclodextrin contained in oral itraconazole solution may decrease asciminib concentrations. Risk X: Avoid combination

Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy

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

Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification

Lonafarnib: May increase the serum concentration of Asciminib. Asciminib may increase the serum concentration of Lonafarnib. Management: Avoid use of lonafarnib with asciminib when possible. If combined, reduce the lonafarnib dose to 115 mg/m2 or continue lonafarnib at a dose of 115 mg/m2. Monitor for both lonafarnib and asciminib toxicities if combined. Risk D: Consider therapy modification

Lornoxicam: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Lornoxicam. Risk C: Monitor therapy

Losartan: CYP2C9 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Losartan. CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Losartan. Risk C: Monitor therapy

Meloxicam: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Meloxicam. Risk C: Monitor therapy

Methadone: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Methadone. Risk C: Monitor therapy

Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy

Mumps- 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 Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Nateglinide: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Nateglinide. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy

OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors): Asciminib may increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

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

Parecoxib: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Parecoxib. Specifically, serum concentrations of the active moiety valdecoxib may be increased. Management: Use the lowest effective dose of parecoxib and consider a dose reduction in patients taking moderate CYP2C9 inhibitors. Risk D: Consider therapy modification

P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Asciminib may increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). 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

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. 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

Ramelteon: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Ramelteon. Risk C: Monitor therapy

Repaglinide: CYP2C8 Inhibitors (Weak) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy

Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

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

Rosuvastatin: Asciminib may increase the serum concentration of Rosuvastatin. Risk X: Avoid combination

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy

Siponimod: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Siponimod. Risk C: Monitor therapy

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

Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy

Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m² when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification

Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

Sulfonylureas: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). 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

Tetrahydrocannabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Specifically, concentrations of tetrahydrocannabinol may be increased. Risk C: Monitor therapy

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Torsemide: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Torsemide. Risk C: Monitor therapy

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy

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

Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification

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

Vitamin K Antagonists (eg, warfarin): CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Voriconazole: Asciminib may increase the serum concentration of Voriconazole. Voriconazole may increase the serum concentration of Asciminib. Risk C: Monitor therapy

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 Interactions

The AUC and C_max of asciminib decreased by 62% and 68%, respectively, with a high-fat meal (1,000 calories, 50% fat) and by 30% and 35%, respectively, with a low-fat meal (400 calories, 25% fat) compared to the fasted state. Management: Administer on an empty stomach.

Reproductive Considerations

Verify pregnancy status prior to use in patients who may become pregnant. Patients who may become pregnant should use effective contraception during therapy and for 1 week after the last asciminib dose.

Changes in menstrual patterns have been reported with tyrosine kinase inhibitor (TKI) therapy (Yu 2019).

Based on the mechanism of action, TKIs have the potential to adversely affect fertility by acting on receptors in the ovaries or testis, primarily when administered prior to puberty in males. Although there are cases showing difficulty conceiving, successful pregnancies have also been reported. Fertility data related to long-term TKI use are limited. Recommendations are available for fertility preservation prior to TKI treatment (ASCO [Oktay 2018]; Madabhavi 2019; Rambhatla 2021).

Patients planning to become pregnant but currently receiving a TKI should minimize the risk of first trimester exposure (Rambhatla 2021). Discontinuing TKI therapy for chronic myeloid leukemia can be considered if the patient is eligible for a tumor-free remission, allowing a washout period before attempting to conceive (Baccarani 2019; ELN [Hochhaus 2020]; Madabhavi 2019). Because the time to conception can be highly variable, treatment may also be discontinued at the first positive pregnancy test, prior to organogenesis in select patients (Abruzzese 2020).

Pregnancy Considerations

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to asciminib may cause fetal harm.

Treatment of chronic myeloid leukemia in pregnant patients should be individualized based on gestational age, hematologic parameters, and clinical condition at presentation. If pregnancy is detected in the first trimester in patients already on a tyrosine kinase inhibitor (TKI), treatment should be discontinued as soon as pregnancy is confirmed. Treatments other than a TKI are recommended in pregnant patients not eligible for a tumor-free remission. If a TKI is needed, use of agents other than asciminib may be considered after the first trimester. Close maternal and fetal monitoring is recommended (Abruzzese 2020; BSH [Smith 2020]; ELN [Hochhaus 2020]; Madabhavi 2019).

The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach (ESMO [Peccatori 2013]).

A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (1-877-635-4499).

Breastfeeding Considerations

It is not known if asciminib is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 1 week after the last asciminib dose. Patients diagnosed with chronic myeloid leukemia requiring a tyrosine kinase inhibitor may consider short-term breastfeeding for the first 2 to 5 days postpartum to provide the benefits of colostrum to the newborn prior to starting or restarting therapy (Abruzzese 2020; Madabhavi 2019).

Monitoring Parameters

CBC every 2 weeks for the first 3 months and monthly thereafter or as clinically necessary; serum lipase and amylase levels monthly or as clinically necessary (monitor more frequently in patients with a history of pancreatitis). Verify pregnancy status prior to use in patients who may become pregnant. Monitor BP; monitor for signs/symptoms of hypersensitivity reactions, myelosuppression, cardiovascular toxicity, and pancreatic toxicity (monitor more frequently in patients with a history of pancreatitis). Monitor adherence.

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; repeat assessment every 3 months for the first year and then every 6 to 12 months thereafter (ASCO [Armenian 2017], ESC [Lyon 2022]). ECG at baseline. Consider baseline echocardiography in all patients; repeat every 3 months for high- and very high-risk patients (ESC [Lyon 2022]).

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.

Mechanism of Action

Asciminib potently inhibits ABL1 kinase activity of the BCR-ABL1 fusion protein via allosteric binding to the ABL myristoyl pocket; it is a STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor (Rea 2021). Asciminib demonstrated activity against wild-type BCR-ABL1 and several mutant forms (including T315I).

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_dss: 151 L.

Protein binding: 97% to plasma proteins.

Metabolism: Primarily hepatic via CYP3A4-mediated oxidation, and UGT2B7- and UGT2B17-mediated glucuronidation.

Half-life elimination: 5.5 hours (40 mg twice daily and 80 mg once daily doses); 9 hours (200 mg twice daily dose).

Time to peak: Median: 2.5 hours (range: 2 to 3 hours).

Excretion: Feces (80%; 57% as unchanged drug); urine (11%; 2.5% as unchanged drug).

Clearance: 6.7 L/hour (40 mg twice daily and 80 mg once daily doses); 4.1 L/hour (200 mg twice daily dose).

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(QA) Qatar: Scemblix

<800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
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Scemblix (asciminib) tablets [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; October 2021.
Scemblix (asciminib) tablets [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; October 2022.
Scemblix (asciminib) [product monograph]. Dorval, Quebec, Canada: Novartis Pharmaceuticals Canada Inc; June 2022.
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Asciminib: Drug information