Ibrutinib—mode of action and appropriate use
Dosing, adjustments and severity grades of adverse events
Special considerations in individual patients
Atrial fibrillation
Clinical risk factors for stroke, TIA and systemic embolism (CHA2DS2-VASc score) | |
---|---|
CHA2DS2-VASc risk factor | Points |
Congestive heart failure Moderate or severe systolic dysfunction and/or recently decompensated heart failure with hospitalization | +1 |
Hypertension Resting blood pressure >140/90 mm Hg on ≥2 occasions or current antihypertensive treatment | +1 |
Age 75 years or older | +2 |
Diabetes mellitus Fasting glucose >125 mg/dL (>7 mmol/L) or treatment with an oral hypoglycemic agent and/or insulin | +1 |
Previous stroke, TIA or thromboembolism | +2 |
Vascular disease Previous myocardial infarction, peripheral artery disease or aortic plaque | +1 |
Age 65–74 years | +1 |
Sex category (female) | +1 |
Bleeding
Clinical characteristics composing the HAS-BLED bleeding risk score | ||
---|---|---|
HAS-BLED risk factor | Points | |
H | Hypertension (resting blood pressure >160 mm Hg systolic) | +1 |
A | Abnormal renal and liver function (1 point each) Chronic dialysis, renal transplantation or serum creatinine >200 µmol/l chronic hepatic disease (e.g., cirrhosis or biochemical evidence of significant hepatic derangement) | +1 or +2 |
S | Stroke (history of stroke or TIA) | +1 |
B | Bleeding (bleeding history or predisposition of bleeding) | +2 |
L | Labile INRs (<60% time in therapeutic range) | +1 |
E | Age >65 years | +1 |
D | Drugs (antiplatelet agents, NSAR) or alcohol abuse (1 point each) | +1 |
Drug-drug interactions (DDI)
Drug class | Substrate |
---|---|
Strong CYP3A4 inhibitors* | |
Antibacterials | Clarithromycin, telithromycin |
Antidepressants | Nefazodone |
Antimycotics | Itraconazole, ketoconazole |
Antivirals | Indinavir, nelfinavir, ritonavir, saquinavir |
Other | Cobicistat, buprenorphine/naloxone |
Moderate CYP3A4 inhibitors | |
Antibacterials | Ciprofloxacin, erythromycin |
Antihypertensives/antiarrhythmics | Amiodarone, diltiazem, dronedarone, verapamil |
Anti-emetics/antinauseants | Aprepitant |
Antimycotics | Fluconazole, voriconazole |
Antineoplastic agents | Crizotinib, imatinib |
Antivirals | Amprenavir, atazanavir, darunavir, fosamprenavir |
Other | Grapefruit juice |
Strong/moderate CYP3A4 inducers* | |
Antibacterials | Rifampicin |
Anti-epileptics | Carbamazepine, phenytoin |
Other | St John’s wort** (Hypericum perforatum) |