Brand Name :
calquence
Synonyms :
acalabrutinib
Class :
Anticoagulant, Bruton’s tyrosine kinase inhibitors
Brand Name :
calquence
Synonyms :
acalabrutinib
Class :
Anticoagulant, Bruton’s tyrosine kinase inhibitors
Dosage Forms & Strengths
Capsule
100mg
Film-coated tablet
100mg
100
mg
Orally
every 12 hrs
chronic lymphocytic leukemia (Cll)
Indicated for monotherapy:
100mg orally every 12 hours
In combination with Obinutuzumab
Cycle 1-Days 1-28: 100mg orally every 12 hours
Cycle 2-Days 1-28: Acalabrutnib-100mg orally every 12 hours
Day 1: Obinutuzumab-100mg intravenous infusion
Day 2: Obinutuzumab-900mg intravenous infusion
Days 8 and 15: Obinutuzumab-1000mg intravenous infusion
Cycle 3-7:
Day 1-28: Acalabrutnib-100mg orally every 12 hours
Day 1: Obinutuzumab-1000mg intravenous infusion
Cycle 8 and later cycles:
Day 1-28: Acalabrutnib-100mg orally every 12 hours
Management of grade adverse ≥3 reactions
• Grade ≥3 nonhematologic toxicities: The drug should be interrupted if the patient experiences grade≥3 nonhematologic toxicities. Once the toxicity resolves to Grade ≤1, the dose should be resumed at 100 mg orally twice a day
• Grade 3 thrombocytopenia with bleeding: The drug should be interrupted if the patient experiences Grade 3 thrombocytopenia with bleeding. Once the toxicity resolves to Grade ≤1, the dose should be resumed at 100 mg orally twice a day
• Grade 4 thrombocytopenia: The drug should be interrupted if the patient experiences Grade 4 thrombocytopenia. Once the toxicity resolves to Grade ≤1, the dose should be resumed at 100 mg orally twice a day
• Grade 4 neutropenia lasting >7 days: If the patient experiences Grade 4 neutropenia lasting longer than seven days, the drug should be interrupted. Once the toxicity resolves to Grade ≤1, the dose should be resumed at 100 mg orally twice a day
• First to the second occurrence: If the same toxicity occurs for a second time, the drug should be interrupted. Once the toxicity resolves to Grade ≤1, the dose should be resumed at 100 mg orally twice a day
• Third occurrence: If the same toxicity occurs for a third time, the drug should be interrupted. Once the toxicity resolves to Grade ≤1, the dose should be reduced to 100 mg orally every day
• Fourth occurrence: If the same toxicity occurs for a fourth time, the drug should be discontinued
Safety and efficacy not established
Refer adult dosing
may reduce the level of serum concentration of acalabrutinib
may reduce the level of serum concentration of acalabrutinib
may reduce the level of serum concentration of acalabrutinib
may reduce the level of serum concentration of acalabrutinib
may reduce the level of serum concentration of acalabrutinib
may decrease the diagnostic effect
may decrease the therapeutic effect of immunosuppressants
may diminish the serum concentration
may diminish the serum concentration
may diminish the serum concentration
may diminish the serum concentration
may diminish the serum concentration
may increase the neutropenic effect of myelosuppressive agents
may diminish the serum concentration
may diminish the serum concentration
may decrease the therapeutic effect of immunosuppressants
may decrease the immunosuppressive effect of immunosuppressants
may decrease the therapeutic effect of immunosuppressants
may increase the myelosuppressive effect of myelosuppressive agents
measles, mumps, rubella, and varicella vaccine, live (Rx)
may decrease the therapeutic effect of immunosuppressants
measles mumps and rubella vaccine, live
may decrease the therapeutic effect of immunosuppressants
may decrease the therapeutic effect of immunosuppressants
vaccinia immune globulin intravenous (Rx)
may decrease the therapeutic effect of immunosuppressants
may decrease the therapeutic effect of immunosuppressants
may diminish the serum concentration
may diminish the serum concentration
may diminish the serum concentration
may diminish the serum concentration of CYP3A4 inducers
may enhance the metabolism of clobetasol propionate
may enhance the serum concentration of CYP3A4 inhibitors
may enhance the serum concentration of CYP3A4 inhibitors
may diminish the serum concentration of CYP3A4 Inducers
It may enhance serum concentration when combined with CYP3A4 Inhibitors (Moderate)
may enhance the serum concentration of CYP3A4 Inhibitor
may increase the immunosuppressive effect of immunosuppressants
may decrease the immunosuppressive effect of immunosuppressants
may increase the immunosuppressive effect of immunosuppressants
may enhance the serum concentration
may enhance the serum concentration
may enhance the serum concentration
may enhance the serum concentration
may enhance the serum concentration
may increase the immunosuppressive effect of immunosuppressants
may increase the immunosuppressive effect of immunosuppressants
may decrease the serum concentration
may decrease the serum concentration
may decrease the serum concentration
may decrease the serum concentration
may decrease the serum concentration
may increase the toxic effect of immunosuppressants
may increase the serum concentration of acalabrutinib
may increase the serum concentration of acalabrutinib
may increase the serum concentration of acalabrutinib
may increase the serum concentration of acalabrutinib
may increase the serum concentration of acalabrutinib
It may diminish the effect when combined with phenobarbital by affecting the intestinal/hepatic enzyme CYP3A4
It may enhance the effect when combined with lonafarnib by affecting CYP3A4 metabolism
It may enhance the effect when combined with grapefruit by CYP3A4 metabolism
the serum concentration of acalabrutinib may be reduced by Inhibitors of the Proton Pump (PPIs and PCABs)
the serum concentration of acalabrutinib may be reduced by Inhibitors of the Proton Pump (PPIs and PCABs)
when both drugs are combined, there may be an increased metabolism of acalabrutinib
when both drugs are combined, there may be an increased effect of acalabrutinib by affecting hepatic or intestinal enzyme cyp3a4 metabolism
when both drugs are combined, there may be a decreased effect of acalabrutinib by affecting hepatic or intestinal enzyme cyp3a4 metabolism
CYP3A strong enhancers of the small intestine may reduce the the bioavailability of acalabrutinib
when both drugs are combined, there may be increase in the serum concentration of acalabrutin
when both drugs are combined, there may be increase in the serum concentration of acalabrutin
may enhance the serum concentration of CYP3A4 inhibitors
may increase the immunosuppressive effect of Immunosuppressants
May may increase the anti-coagulant action when combined.
may increase the toxic effect of myelosuppressive agents
may increase the myelosuppressive effect of myelosuppressive agents
may increase the myelosuppressive effect of myelosuppressive agents
may increase the antiplatelet effect of antiplatelet agents
may increase the antiplatelet effect of antiplatelet agents
may increase the antiplatelet effect of antiplatelet agents
may increase the antiplatelet effect of antiplatelet agents
may increase the antiplatelet effect of antiplatelet agents
may increase the immunosuppressive effect of immunosuppressants
may decrease the therapeutic effect of immunosuppressants
may decrease the therapeutic effect of immunosuppressants
may increase the antiplatelet effect of antiplatelet agents
may increase the antiplatelet effect of antiplatelet agents
may increase the antiplatelet effect of antiplatelet agents
May have an increased antiplatelet effect when combined with Antiplatelet agents
may have an increased anticoagulant effect when combined with anticoagulants
may have an increased anticoagulant effect when combined with anticoagulants
may have an increased anticoagulant effect when combined with anticoagulants
may have an increased anticoagulant effect when combined with anticoagulants
may have an increased anticoagulant effect when combined with anticoagulants
By synergism effects, the toxicity of the other drug increases.
when both drugs combine the risk of both drug increases the toxicity of other by synergism.
both drug toxicity increases by synergism action.
Increased risk of myelosuppressive effects.
increase myelosuppressive effects by increasing serum concentration of daunorubicin
the synergistic effect is shown between acalabrutinib and mercaptopurine, leading to an increased risk of myelosuppression risk of infection increases on administering both the drugs simultaneously adalimumab: synergistic effect; causing immunosuppression risk of infection increases on administering both the drugs simultaneously
the levels of lenvanitib are increased by acalabrutinib or vice-versa.
increase the risk of myelosuppressive effects by pharmacodynamic synergism
when both drugs are combined, there may be an increased risk or severity of adverse effects
the effect of acalabrutinib is decreased by lorlatinib, by altering intestinal or hepatic CYP3A4 enzyme metabolism
when used in combination, both the drugs increase the toxic levels of one another through synergistic activity
increase the risk of myelosuppressive effects by pharmacodynamic synergism
either of the drugs, when used in combination, increases the toxicity due to synergistic activity
The interaction may enhance the myelosuppressive effects
when both drugs are combined, there may be a reduced blood level of acalabrutinib
increase myelosuppressive effects by increasing serum concentration of idarubicin
metronidazole enhances the effect of acalabrutinib by altering the intestinal or hepatic CYP3A4 enzyme metabolism
may increase the anti-platelet effect
may increase the anti-coagulant action of anti-coagulants
may increase the antiplatelet effect of antiplatelet agents
may increase the anticoagulant effect of Anticoagulants
It may enhance toxicity when combined with albendazole by pharmacodynamic synergism
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
may increase the levels of serum concentration
Mechanism of action
It is a selective, oral, second-generation Bruton’s tyrosine kinase (BTK) inhibitor. The mechanism of action of acalabrutinib is the inhibition of BTK, an enzyme involved in the B-cell activation signaling pathway, leading to decreased proliferation and survival of B-cells
Spectrum
The spectrum of activity of acalabrutinib is primarily in hematologic malignancies, such as mantle cell lymphoma and chronic lymphocytic leukemia (CLL). It has also shown efficacy in other B-cell lymphomas
Frequency defined:
>10%
All grades
Decreased platelets
Decreased neutrophils
Fatigue
Bruising
Rash
Constipation
Decreased hemoglobin
Headache
Diarrhea
Myalgia
Nausea
Abdominal pain
Grade≥3
Decreased neutrophils
Decreased hemoglobin
Vomiting
Decreased platelets
1-10%
All grades
Neutropenia
Thrombocytopenia
Upper respiratory tract infection
Musculoskeletal pain
Bruising
Diarrhea
Rash
Arthralgia
Nausea
Urinary tract infection
Anemia
Headache
Increased AST
Fatigue
Increased ALT
Increased uric acid
Dizziness
Hemorrhage
Increased bilirubin
Grade ≥3
Increased uric acid
Anemia
Lymphocytosis
Neutropenia
Infection
thrombocytopenia
<1%
All grades
Epistaxis
Hemorrhage
Grade ≥3
Increased AST
Headache
Vomiting
Increased ALT
Diarrhea
Abdominal pain
1-10% (In combination with Obinutuzumab)
Grade ≥3
Diarrhea
Fatigue
Musculoskeletal pain
Arthralgia
Lower respiratory tract infections
upper respiratory tract infections
rash
hemorrhage
headache
<1%(Monotherapy)
Grade ≥3
Fatigue
rash
hemorrhage
nausea
myalgia
Post-marketing reports
Opportunistic infections
Contraindications
None
Caution
Pregnancy consideration: It may cause foetal harm when administered
Pregnancy category: D
Lactation: Excretion of the drug in human breast milk is unknown
Pregnancy category:
Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.
Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.
Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.
Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.
Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.
Category N: There is no data available for the drug under this category
Pharmacology
It selectively inhibits Bruton’s tyrosine kinase (BTK), a signaling molecule in the B-cell antigen receptor (BCR) and cytokine receptor pathways. Inhibition of BTK results in the suppression of B-cell activation, proliferation, trafficking, chemotaxis, and adhesion.
acalabrutinib and its active metabolite, ACP-5862, form a covalent bond with a cysteine residue in the BTK active site, which leads to long-lasting inhibition of BTK enzymatic activity. This specific mechanism of action makes acalabrutinib a selective and potent BTK inhibitor.
Pharmacodynamics
The pharmacodynamics of acalabrutinib can be described as follows:
Pharmacokinetics
Absorption
Distribution
Metabolism
Elimination/excretion
Administration
It is administered orally as either a capsule or a tablet. The recommended dose is 100 mg taken orally twice daily until disease progression or unacceptable toxicity occurs. The capsule and tablet are bioequivalent, and food does not affect the bioavailability of acalabrutinib
Patient information leaflet
Generic Name: acalabrutinib
Pronounced: [ a-KAL-a-BROO-ti-nib ]
Why do we use acalabrutinib?
It is a medication used to treat several types of cancer, including: