asciminib

Absorption: Well absorbed following oral administration. Absorption ↓ by food.

Distribution: Extensively distributed to tissues.

Protein Binding: 97%.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP3A4 isoenzyme and via glucuronidation. 80% excreted in the feces (57% as unchanged drug), with 11% excreted in the urine (2.5% as unchanged drug). Also eliminated by biliary secretion by the breast cancer–resistant protein (BCRP).

Half-Life: 40 mg twice daily or 80 mg once daily: 5.5 hr; 200 mg twice daily: 9 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2–3 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

History of pancreatitis;
History of or risk factors for cardiovascular disease;
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema, hypertension, arterial thromboembolism, myocardial ischemia, ARRHYTHMIAS, HF, palpitations, QT interval prolongation

Derm: rash, pruritus, urticaria

EENT: blurred vision, dry eye

Endo: hypothyroidism

F and E: hyperkalemia, hyperphosphatemia, hypocalcemia, hypokalemia, hypophosphatemia

GI: abdominal pain, diarrhea, hyperbilirubinemia, ↑amylase, ↑lipase, ↑liver enzymes, nausea, vomiting, constipation, ↓appetite, pancreatitis

GU: ↑serum creatinine, ↓fertility (females), urinary tract infection

Hemat: anemia, bleeding, lymphopenia, neutropenia, thrombocytopenia

Metab: hypercholesterolemia, hypertriglyceridemia, hyperuricemia

MS: arthralgia, ↑creatine kinase, pain

Neuro: cerebral ischemia, fatigue, headache, dizziness, peripheral neuropathy

Resp: cough, upper respiratory tract infection, dyspnea, lower respiratory tract infection, pleural effusion

Misc: hypersensitivity reactions, fever, influenza

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including clarithromycin, may ↑ levels and risk of toxicity; closely monitor patients using asciminib 200 mg twice daily.
Itraconazole (oral solution) containing hydroxypropyl-β-cyclodextrin may ↓ levels and effectiveness; avoid concurrent use.
May ↑ levels and risk of toxicity of CYP3A4 substrates, including midazolam; closely monitor when using asciminib 40 mg twice daily or 80 mg once daily. Avoid concurrent use with asciminib 200 mg twice daily.
May ↑ levels and risk of toxicity of CYP2C9 substrates, including warfarin; avoid concurrent use with asciminib 40 mg twice daily or 80 mg once daily; if concurrent use unavoidable, ↓ dose of CYP2C9 substrate. Avoid concurrent use with asciminib 200 mg twice daily; if concurrent use unavoidable, use non-CYP2C9 substrate.
May ↑ levels and risk of toxicity of P-glycoprotein substrates; closely monitor.
May ↑ levels and risk of toxicity of breast cancer–resistance protein (BRCP) substrates and OATP1B substrates, including atorvastatin and rosuvastatin; avoid concurrent use with atorvastatin or rosuvastatin.

Route/Dosage ⬆ ⬇

Philadelphia Chromosome–Positive Chronic Myeloid Leukemia in Chronic Phase Previously Treated with 2 Tyrosine Kinase Inhibitors

PO (Adults ): 80 mg once daily or 40 mg every 12 hr.

Philadelphia Chromosome–Positive Chronic Myeloid Leukemia in Chronic Phase with the T315I Mutation

PO (Adults ): 200 mg every 12 hr.

Availability ⬆ ⬇

Film-coated tablets: 20 mg; 40 mg

Assessment ⬆ ⬇

Assess for fever, infection, or signs and symptoms suggestive of bleeding or easy bruising. May indicate myelosuppression.
Assess respiratory status and for upper respiratory tract infection (nasopharyngitis, rhinitis, pharyngitis, and pharyngotonsillitis).
Assess musculoskeletal pain (pain in extremities, back pain, myalgia, noncardiac chest pain, neck pain, bone pain, spinal pain, arthritis).
Monitor for nausea, vomiting, severe abdominal pain, or abdominal discomfort, especially in patients with a history of pancreatitis.
Monitor BP and assess for confusion, headache, dizziness, chest pain, or shortness of breath and manage hypertension using standard antihypertensive therapy during treatment as clinically indicated.
Assess for signs and symptoms of hypersensitivity (rash, edema, and bronchospasm). Initiate appropriate treatment.
Monitor patients with history of cardiovascular risk factors for cardiovascular signs and symptoms. Initiate appropriate treatment as clinically indicated. For ≥Grade 3 cardiovascular toxicity, temporarily withhold asciminib, resume at reduce dose, or permanently discontinue depending on persistence of toxicity.

Lab Test Considerations:

Verify the pregnancy status of females of reproductive potential prior to starting treatment.
Perform CBC every 2 wk for the first 3 mo of treatment, then monthly or as clinically indicated. May cause decreased platelet count , ANC, and hemoglobin. If ANC ≤1,000/mm³and/or platelets ≤50,000/mm³, withhold therapy until ANC and platelets return above these values. If resolved within 2 wk, resume at starting dose. If problem takes >2 wk to resolve, resume at reduced dose.
Assess serum lipase and amylase levels monthly during treatment and as clinically indicated. May cause increased CK, ALT, lipase, amylase, and triglycerides. If lipase and/or amylase are elevated ≥2 × upper limit of normal (ULN) and patient is asymptomatic, withhold therapy until resolved to ≤1.5 × ULN. Once resolved, resume at reduced dose. If events reoccur at reduced dose, permanently discontinue. If not resolved, permanently discontinue therapy and perform diagnostic tests to exclude pancreatitis.

Implementation ⬆ ⬇

Heightened risk of causing significant patient harm when used in error. Use safe medication administration practices.
PO: Dose Reductions for Adverse Reactions for Ph+ CML in Chronic Phase, Previously Treated with Two or More Tyrosine Kinase Inhibitors: Reduce dose to 40 mg once daily or 20 mg twice daily. Permanently discontinue if unable to tolerate reduction.
Dose Reductions for Adverse Reactions for Ph+ CML in Chronic Phase with the T315I Mutation:Reduce dose to 160 mg twice daily. Permanently discontinue if unable to tolerate reduction.
DNC: Swallow tablets whole. Do not break, crush, or chew the tablets.
Administer without food. Avoid food for ≥2 hr before and 1 hr after taking the medication.
May cause reproductive toxicity, teratogenicity, and a toxicity profile similar to existing hazardous agents. Wear chemotherapy gloves, gown, and eye/face protection while administrating.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Instruct patient to take the medication exactly as prescribed. If patients taking once daily miss a dose by >12 hr, skip the missed dose. If patients taking twice daily miss a dose by >6 hr, skip the missed dose. Do not change the dose, schedule, or stop taking it unless told to do so by an health care professional.
Instruct patient to immediately report any signs or symptoms of myelosuppression to a health care professional.
Instruct patient to contact a health care professional for elevated BP or symptoms of hypertension.
Advise patient to report signs and symptoms of pancreatic toxicity to a health care professional immediately.
Instruct the patient to discontinue asciminib and seek immediate medical attention if any signs or symptoms of a hypersensitivity reaction occur.
Instruct patient to immediately contact a health care provider or get medical help if cardiovascular toxicity signs and symptoms develop.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 1 wk after last dose. Do not breastfeed during treatment and for 1 wk after the last dose. Advise patient to notify health care professional promptly if pregnancy is suspected.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇