Posology : מינונים

5. DOSAGE AND ADMINISTRATION

5.1 Recommended Dosage
The recommended dosage of BRUKINSA is 160 mg taken orally twice daily or 320 mg taken orally once daily until disease progression or unacceptable toxicity.
BRUKINSA can be taken with or without food. Advise patients to swallow capsules whole with water. Advise patients not to open, break, or chew the capsules. If a dose of BRUKINSA is missed, it should be taken as soon as possible on the same day with a return to the normal schedule the following day.
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5.2 Dosage Modification for Use in Hepatic Impairment
The recommended dosage of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily [see Use in Specific Populations (11.7) and Clinical Pharmacology (13.3)].
5.3 Dosage Modifications for Drug Interactions
Recommended dosage modifications of BRUKINSA for drug interactions are provided in Table 1
[see Drug Interactions (10.1)].
Table 1:                   Dose Modifications for Use with CYP3A Inhibitors or Inducers 

Coadministered Drug                     Recommended BRUKINSA Dosage


80 mg once daily
Strong CYP3A inhibitor                  Interrupt dose as recommended for adverse reactions [see Dosage and Administration (5.4)].
80 mg twice daily
Moderate CYP3A inhibitor                Modify dose as recommended for adverse reactions [see Dosage and Administration (5.4)].
Moderate or strongCYP3A inducer         Avoid concomitant use.


After discontinuation of a CYP3A inhibitor, resume previous dose of BRUKINSA [see Dosage and Administration (5.1, 5.2) and Drug Interactions (10.1)].
5.4 Dosage Modifications for Adverse Reactions
Recommended dose modifications of BRUKINSA for Grade 3 or higher adverse reactions are provided in Table 2:
Table 2:                 Recommended Dosage Modification for Adverse Reaction Adverse Reaction                      Adverse Reaction     Dosage Modification Occurrence           (Starting Dose: 160 mg twice daily or
320 mg once daily)
Hematological toxicities [see Warnings and Precautions (8.3)]
Interrupt BRUKINSA
Once toxicity has resolved to Grade 1 or
First                lower or baseline: Resume at 160 mg
Grade 3 febrile neutropenia twice daily or 320 mg once daily

Grade 3 thrombocytopenia with                              Interrupt BRUKINSA significant bleeding                                       Once toxicity has resolved to Grade 1 or Second               lower or baseline: Resume at 80 mg twice daily or 160 mg once daily

Grade 4 neutropenia(lasting more than 10 consecutive days)
Interrupt BRUKINSA
Once toxicity has resolved to Grade 1 or
Grade 4 thrombocytopenia (lasting     Third                lower or baseline: Resume at 80 mg once more than 10 consecutive days)                             daily



Fourth               Discontinue BRUKINSA
Non-hematological toxicities [see Warnings and Precautions (8.5) and Adverse Reactions (9.1)] Grade 3 or 4 non-hematological                             Interrupt BRUKINSA toxicities *                                               Once toxicity has resolved to Grade 1 or First                lower or baseline: Resume at 160 mg twice daily or 320 mg once daily^
Adverse reaction                            Adverse Reaction        Dosage Modification Occurrence              (Starting Dose: 160 mg twice daily or
320 mg once daily)
Interrupt BRUKINSA
Once toxicity has resolved to Grade 1 or
Second                  lower or baseline: Resume at 80 mg twice daily or 160 mg once daily
Interrupt BRUKINSA
Once toxicity has resolved to Grade 1 or
Third                   lower or baseline: Resume at 80 mg once daily
Fourth                  Discontinue BRUKINSA
*Evaluate the benefit-risk before resuming treatment for a Grade 4 non-hematological toxicity.
^ Evaluate the benefit-risk before resuming treatment at the same dosage for Grade 4 non-hematological toxicity
Asymptomatic lymphocytosis should not be regarded as an adverse reaction, and these patients should continue taking BRUKINSA.


6. DOSAGE FORMS AND STRENGTHS
Capsules: Each 80 mg capsule is a size 0, white to off-white opaque capsule marked with “ZANU 80” in black ink.


6.1. List of Excipients:
Microcrystalline cellulose, Croscarmellose sodium, Sodium lauryl sulphate, Colloidal silicon dioxide, Magnesium stearate
Capsule Shell : Gelatin ,Titanium Dioxide. Imprinting Ink(traces)