Posology : מינונים

5. DOSAGE AND ADMINISTRATION
5.1 Recommended Dosage
CALQUENCE CAPSULES as Monotherapy
For patients with MCL, CLL, or SLL, the recommended dose of CALQUENCE CAPSULES is 100 mg taken orally approximately every twelve hours until disease progression or unacceptable toxicity.


CALQUENCE CAPSULES in Combination with Obinutuzumab
For patients with previously untreated CLL or SLL, the recommended dose of CALQUENCE CAPSULES is 100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity. Start CALQUENCE CAPSULES at Cycle 1 (each cycle is 28 days). Start obinutuzumab at Cycle 2 for a total of 6 cycles and refer to the obinutuzumab prescribing information for recommended dosing. Administer CALQUENCE CAPSULES prior to obinutuzumab when given on the same day.
Advise patients to swallow capsule whole with water. Advise patients not to open, break or chew the capsules. CALQUENCE CAPSULES may be taken with or without food. If a dose of CALQUENCE CAPSULES is missed by more than 3 hours, it should be skipped and the next dose should be taken at its regularly scheduled time. Extra capsules of CALQUENCE CAPSULES should not be taken to make up for a missed dose.


5.2 Recommended Dosage for Hepatic Impairment
Avoid administration of CALQUENCE CAPSULES in patients with severe hepatic impairment.
Dose modifications are not required for patients with mild or moderate hepatic impairment [see Use in Specific Populations (11.6) and Clinical Pharmacology (13.3)].


5.3 Recommended Dosage for Drug Interactions
Dose Modifications for Use with CYP3A Inhibitors or Inducers
These are described in Table 1 [see Drug Interactions (10)].

Table 1: Recommended Dose Modifications for Use with CYP3A Inhibitors or Inducers CYP3A                     Co-administered Drug            Recommended CALQUENCE CAPSULES use
Inhibition                Strong CYP3A inhibitor          Avoid concomitant use.
If these inhibitors will be used short- term (such as anti-infectives for up to seven days), interrupt CALQUENCE
CAPSULES.
Moderate CYP3A inhibitor        100 mg once daily.
Induction                 Strong CYP3A inducer            Avoid concomitant use.
If these inducers cannot be avoided,
increase CALQUENCE CAPSULES dose to 200 mg approximately every
12 hours.


Concomitant Use with Gastric Acid Reducing Agents
Proton Pump Inhibitors: Avoid concomitant use [see Drug Interactions (10)].
H2-Receptor Antagonists: Take CALQUENCE CAPSULES 2 hours before taking a H2-receptor antagonist [see Drug Interactions (10)].
Antacids: Separate dosing by at least 2 hours [see Drug Interactions (10)].
5.4 Dose Modifications for Adverse Reactions
Recommended dose modifications of CALQUENCE CAPSULES for Grade 3 or greater adverse reactions are provided in Table 2.


Table 2: Recommended Dose Modifications for Adverse Reactions
Event                               Adverse           Dose Modification Reaction          (Starting dose = 100 mg approximately
Occurrence        every
12 hours)
First and         Interrupt CALQUENCE CAPSULES.
Grade 3 or greater non-             Second hematologic toxicities,                               Once toxicity has resolved to Grade 1 or baseline level, CALQUENCE CAPSULES
Grade 3 thrombocytopenia                              may be resumed at 100 mg approximately with bleeding,                                        every 12 hours.
Third             Interrupt CALQUENCE CAPSULES.
Grade 4 thrombocytopenia or                                                    Once toxicity has resolved to Grade 1 or Grade 4 neutropenia lasting                           baseline level, CALQUENCE CAPSULES longer than 7 days                                    may be resumed at a reduced frequency of 100 mg once daily.
Fourth            Discontinue CALQUENCE CAPSULES.


Refer to the obinutuzumab prescribing information for management of obinutuzumab toxicities.

6. DOSAGE FORMS AND STRENGTHS
100 mg capsules.