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3._RA_NSS_Scemblix_v2.1_SLC1394s+1411s+NI_Oct_2024_CLN.pdf
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Regulatory Affairs

 

SCEMBLIX™ (asciminib)

20 mg and 40 mg Film-coated tablets

 

National Succinct Statement (NSS)

 

 

 

 

Version 2.1

 

                                    Effective date:                                      31-May-2024

                                   Safety Label Change (SLC)                  2023-PSB/GLC-1394-s + 2024-PSB/GLC-1411-s + NI

                                   Tracking number:

                                Document status:                                  Final

 

 

 

Property of Novartis Confidential

May not be used, divulged, published or otherwise disclosed

without the consent of Novartis

 

 

 

 

SCEMBLIX™

Important note: Before prescribing, consult full prescribing information: https://www.fda.gov/.

Disclaimer: This link will contain the most updated product information approved by the reference country.

 

Presentation: Film-coated tablets containing 21.62 mg and 43.24 mg of asciminib hydrochloride, corresponding to 20 mg and 40 mg of asciminib.

 

Indications: SCEMBLIX is indicated for the treatment of adult patients with:

 

• Newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP).

This indication is approved under accelerated approval based on major molecular response rate [see Clinical Studies (14.1)]. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial(s).

• Previously treated Ph+ CML in CP.

• Ph+ CML in CP with the T315I mutation.

 

Dosage and administration:

  Recommended Dosage in Patients with Newly Diagnosed or Previously Treated Ph+ CML-CP

The recommended dose of SCEMBLIX is 80 mg taken orally once daily at approximately the same time each day or 40 mg orally twice daily at approximately 12-hour intervals. The recommended dose of SCEMBLIX is taken orally without food. Avoid food consumption for at least 2 hours before and 1 hour after taking SCEMBLIX [see Clinical Pharmacology (12.2)].

Continue treatment with SCEMBLIX as long as clinical benefit is observed or until unacceptable toxicity occurs.

 

Recommended Dosage in Patients with Ph+ CML-CP with the T315I Mutation

The recommended dose of SCEMBLIX is 200 mg taken orally twice daily at approximately 12-hour intervals. The recommended dose of SCEMBLIX is taken orally without food. Avoid food consumption for at least 2 hours before and 1 hour after taking SCEMBLIX [see Clinical Pharmacology (12.2)].

 

Missed Dose

Once Daily Dosage Regimen: If a SCEMBLIX dose is missed by more than approximately 12 hours, skip the dose and take the next dose as scheduled.

Twice Daily Dosage Regimens: If a SCEMBLIX dose is missed by more than approximately 6 hours, skip the dose and take the next dose as scheduled.

 

Dosage Modifications

Dosage Modifications for Patients with Newly Diagnosed or Previously Treated Ph+ CML-CP For the management of adverse reactions, reduce the SCEMBLIX dose as described in Table 1. Dosage Modifications for Patients with Ph+ CML-CP with the T315I Mutation

For the management of adverse reactions, reduce the SCEMBLIX dose as described in Table 1.

 

Table 1: Recommended Dosage Reductions for SCEMBLIX for Adverse Reactions

 

Dosage reduction

Dosage for Patients with newly diagnosed or previously treated Ph+ CML-CP

Dosage for patients with Ph+ CML- CP with the T315I mutation

First

• 40 mg once daily
OR
• 20 mg twice daily

160 mg twice daily

Subsequent reduction

Permanently discontinue SCEMBLIX in patients unable to tolerate 40 mg once daily OR 20 mg twice daily.

Permanently discontinue SCEMBLIX in patients unable to tolerate 160 mg twice daily.

 

The recommended dosage modifications for the management of selected adverse reactions are shown in Table 2.

Table 2: SCEMBLIX Dosage Modification for the Management of Adverse Reactions

 

Adverse reaction

Dosage modification

Thrombocytopenia and/or neutropenia [see Warnings and Precautions (5.1)]

ANC less than 1 x 109/L and/or PLT less than 50 x 109/L

Withhold SCEMBLIX until resolved to ANC greater than or equal to 1 x 109/L and/or PLT greater than or equal to 50 x 109/L.
If resolved:
• Within 2 weeks: resume SCEMBLIX at starting dose.
• After more than 2 weeks: resume SCEMBLIX at reduced dose.
For recurrent severe thrombocytopenia and/or neutropenia, withhold SCEMBLIX until resolved to ANC greater than or equal to 1 x 109/L and PLT greater than or equal to 50 x 109/L, then resume at reduced dose.

Asymptomatic amylase and/or lipase elevation [see Warnings and Precautions (5.2)]

Elevation greater than 2 x ULN

Withhold SCEMBLIX until resolved to less than
1.5 x ULN.
If resolved:
• Resume SCEMBLIX at reduced dose. If events reoccur at reduced dose, permanently discontinue SCEMBLIX.
If not resolved:
• Permanently discontinue SCEMBLIX. Perform diagnostic tests to exclude pancreatitis.

Non-hematologic adverse reactions [see Warnings and Precautions (5.3, 5.4, 5.5)]

Grade 3a or higher

Withhold SCEMBLIX until recovery to Grade 1 or less.
If resolved:
• Resume SCEMBLIX at reduced dose.
If not resolved:
• Permanently discontinue SCEMBLIX.
Abbreviations: ANC, absolute neutrophil count; PLT, platelets; ULN, upper limit of normal.
aBased on Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

 

Administration

Advise patients to swallow SCEMBLIX tablets whole. Do not break, crush, or chew the tablets.

Contraindications: None.

 

Warnings and precautions:

♦ Myelosuppression: Complete blood counts should be performed every 2 weeks for first 3 months and monthly thereafter. Patients should be monitored for signs and symptoms of myelosuppression. Dose reduction, temporarily withholding or permanent discontinuation should be based on severity of thrombocytopenia and/or neutropenia. ♦Pancreatic toxicity: Serum lipase and amylase should be assessed monthly, and patients monitored for signs and symptoms of pancreatic toxicity. More frequent monitoring in patients with a history of pancreatitis recommended. If enzymes elevation accompanied by abdominal symptoms, temporary withholding treatment and diagnostic tests recommended. Dose reduction, temporarily withholding or permanent discontinuation should be based on severity of lipase and amylase elevation. ♦QT prolongation: Monitor patients with history of cardiovascular risk factors for cardiovascular signs and symptoms. Initiate appropriate treatment as clinically indicated; for Grade 3 or higher cardiovascular toxicity, temporarily withhold, reduce dose, or permanently discontinue SCEMBLIX depending on persistence of cardiovascular toxicity. ♦Hypertension: Patients should be monitored for signs and symptoms of hypertension. Management of hypertension with standard therapy during Scemblix treatment recommended. ♦Hypersensitivity: Patients should be monitored for signs and symptoms of hypersensitivity. Initiation of appropriate treatment recommended. ♦Embryo-fetal toxicity: Scemblix can cause fetal harm. Advising pregnant women and females of reproductive potential of the potential risk to a fetus. Pregnancy status verification prior to the start of Scemblix treatment in females of reproductive potential. Sexually active females of reproductive potential should use effective contraception during Scemblix treatment and for at least 3 days after the last dose.

Pregnancy, lactation, females of reproductive potential:

Pregnancy: Scemblix can cause embryo-fetal harm. Advising pregnant women and females of reproductive potential of the potential risk to a fetus.

Lactation: Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with SCEMBLIX and for 1 week after the last dose.

Females and males of reproductive potential: Pregnancy testing: Pregnancy status verification prior to the start of Scemblix treatment in females of reproductive potential. ♦Contraception: Sexually active females of reproductive potential should use effective contraception during Scemblix treatment and for at least 1 week after the last dose.

Infertility: Based on findings in animals, SCEMBLIX may impair fertility in females of reproductive potential. The reversibility of the effect on fertility is unknown.

 

Adverse drug reactions:

Very common (≥10%): Upper respiratory tract infection, thrombocytopenia, neutropenia, anaemia, dyslipidaemia, headache, dizziness, hypertension, cough, pancreatic enzymes increased, vomiting, diarrhoea, nausea, abdominal pain, hepatic enzyme increased, rash, pruritus, musculoskeletal pain, arthralgia, fatigue, edema, hemorrhage.

Clinically relevant adverse reactions in < 10%: arthralgia, constipation, nausea, hypertension, cough, pruritus, dry eye, pyrexia, vomiting, dizziness, edema, lower respiratory tract infection, decreased appetite, hypothyroidism, urticaria, arrhythmia, influenza, neuropathy peripheral, hemorrhage, urinary tract infection, pneumonia, dyspnea, pancreatitis, vision blurred, febrile neutropenia, and palpitations.

Interactions: ♦Scemblix 200 mg twice daily dose: Caution recommended with CYP3A4 inhibitors. ♦All Scemblix doses: Caution recommended with strong CYP3A4 inducers. ♦All Scemblix doses: Caution recommended with CYP3A4 substrates with narrow therapeutic index. ♦All Scemblix doses: Caution recommended with substrates of OATP1B, BCRP or both transporters. Reference to these substrates’ dose reductions should be made. Avoid co-administration with rosuvastatin and consider alternative statins. ♦All Scemblix doses: Caution recommended with P-gp substrates of narrow therapeutic index.

Packs and prices: Country-specific.

Legal classification: Country-specific.

Leaflet revision date: October 2024.

NSS version number: 2.1

Leaflet presentation: R02.

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