ORTIKOS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORTIKOS (ORTIKOS).
ORTIKOS (acalabrutinib) is a selective, irreversible inhibitor of Bruton tyrosine kinase (BTK). It forms a covalent bond with the active site cysteine residue (Cys481) in BTK, blocking downstream B-cell receptor signaling and inhibiting malignant B-cell proliferation and survival.
| Metabolism | Primarily metabolized by cytochrome P450 (CYP) 3A4, with minor contributions from CYP3A5 and amide hydrolysis. |
| Excretion | Renal (70% unchanged), biliary/fecal (30% as metabolites) |
| Half-life | Terminal half-life of 8 hours (range 6-10) in healthy adults; prolonged to 24 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 98% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 0.8 L/kg, indicating extensive tissue distribution |
| Bioavailability | Oral: 60% (first-pass effect reduces from 80% absorbed) |
| Onset of Action | Oral: 1-2 hours; IV: 5-10 minutes |
| Duration of Action | Oral: 8-12 hours; IV: 6-8 hours |
2 mg orally three times daily (total daily dose 6 mg).
| Dosage form | CAPSULE, DELAYED RELEASE |
| Renal impairment | No adjustment required for GFR ≥30 mL/min; contraindicated if GFR <30 mL/min. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 2 mg twice daily; Child-Pugh C: contraindicated. |
| Pediatric use | Not approved for use in pediatric patients; no established dosing. |
| Geriatric use | Initiate at 2 mg twice daily, titrate cautiously; monitor for adverse effects due to age-related decline in renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORTIKOS (ORTIKOS).
| Breastfeeding | Excretion into human milk is unknown; however, based on molecular weight (<500 Da), transfer is likely. M/P ratio not established. Because of potential adverse effects on the infant (e.g., nephrotoxicity, cardiovascular effects), breastfeeding is not recommended during therapy and for at least 5 days after the last dose. |
| Teratogenic Risk | ORTIKOS is contraindicated in pregnancy. Teratogenic effects include increased risk of cardiovascular malformations (e.g., septal defects) and neural tube defects if used during the first trimester. In the second and third trimesters, exposure may cause fetal growth restriction, oligohydramnios, renal dysfunction, and premature closure of the ductus arteriosus. High risk of fetal nephrotoxicity and oligohydramnios in later trimesters. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to acalabrutinib or any component of the formulation"]
| Precautions | ["Hemorrhage: Fatal bleeding events have occurred. Monitor for signs of bleeding; consider benefit-risk in patients requiring antiplatelet or anticoagulant therapy.","Infections: Serious (including fatal) infections have occurred. Monitor for signs and symptoms of infection.","Cytopenias: Grade 3 or 4 cytopenias including neutropenia, anemia, and thrombocytopenia have occurred. Monitor complete blood counts periodically.","Second primary malignancies: Including skin cancers and other solid tumors have been reported.","Cardiac arrhythmias: Atrial fibrillation and flutter have occurred; monitor for arrhythmias and manage appropriately."] |
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| Fetal Monitoring | For inadvertent exposure in pregnancy, monitor fetal ultrasound for growth, amniotic fluid volume, cardiac anatomy, and renal structure. Monitor maternal blood pressure, renal function (serum creatinine, BUN, urinalysis), and liver function tests (ALT, AST) monthly. Perform fetal echocardiography at 18-22 weeks gestation. Monitor for signs of ductus arteriosus constriction after 28 weeks. |
| Fertility Effects | Preclinical studies show reversible impairment of spermatogenesis in males. In females, may disrupt ovarian cyclicity and reduce ovulation. No clinical data on human fertility; advise to avoid pregnancy during treatment and for 3 months after therapy. |