Posology : מינונים

3       DOSAGE AND ADMINISTRATION
3.1    Patient Selection
Select patients for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer with TRUQAP, based on the presence of one or more of the following genetic alterations in tumor tissue: PIK3CA/AKT1/PTEN [see Clinical Studies (13)].
3.2     Recommended Evaluation Before Initiating TRUQAP

Evaluate fasting blood glucose (FG) and hemoglobin A1C (HbA1C) prior to starting TRUQAP and at regular intervals during treatment [see Warnings and Precautions (6)].


3.3     Recommended Dosage and Administration
The recommended dosage of TRUQAP, in combination with fulvestrant, is 400 mg orally twice daily (approximately 12 hours apart) with or without food, for 4 days followed by 3 days off. Continue TRUQAP until disease progression or unacceptable toxicity. TRUQAP dosing schedule for each week is provided in Table 1.


Table 1: TRUQAP Dosing Schedule for Each Week

Day                1            2            3             4            5*         6*         7* 
Morning       2 x 200 mg 2 x 200 mg 2 x 200 mg         2 x 200 mg

Evening       2 x 200 mg 2 x 200 mg 2 x 200 mg         2 x 200 mg
* No dosing on day 5, 6 and 7.

Swallow TRUQAP tablets whole. Do not chew, crush, or split tablets prior to swallowing. Do not take tablets that are broken, cracked, or otherwise not intact.

If a patient misses a dose within 4 hours of the scheduled time, instruct the patient to take the missed dose.

If a patient misses a dose more than 4 hours of the scheduled time, instruct the patient to skip the dose and take the next dose at its usual scheduled time.

If a patient vomits a dose, instruct the patient not to take an additional dose and take the next dose at its usual scheduled time.

Refer to the fulvestrant Full Prescribing Information for recommended fulvestrant dosing information.

For premenopausal and perimenopausal women, administer a luteinizing hormone-releasing hormone (LHRH) agonist according to current clinical practice standards.

For men, consider administering a LHRH agonist according to current clinical practice standards.
3.4    Dosage Modifications for Adverse Reactions

The recommended dose reductions for adverse reactions are listed in Table 2.
Permanently discontinue TRUQAP if unable to tolerate the second dose reduction.


Table 2. Recommended Dose Reductions of TRUQAP for Adverse Reactions
TRUQAP                        Dose and Schedule
First dose reduction          320 mg twice daily for 4 days followed by 3 days off Second dose reduction         200 mg twice daily for 4 days followed by 3 days off 

The recommended dosage modifications for adverse reactions are provided in Table 3.
Table 3: Recommended Dosage Modifications of TRUQAP for Adverse Reactions 
Adverse Reaction Severity*             TRUQAP Dosage Modification

Hyperglycemia      FG >                Consider initiation or intensification of oral antidiabetic ULN-160 mg/dL       treatment.
(Fasting Glucose or
FG >
[FG]) [see         ULN-8.9 mmol/L
Warnings and       or
HbA1C > 7%
Precautions (6.1)]
FG 161-250 mg/dL Withhold TRUQAP until FG decrease < 160 mg/dL (or < or               8.9 mmol/L)
FG 9-13.9 mmol/L
If recovery occurs in < 28 days, resume TRUQAP at same dose.
If recovery occurs in > 28 days, resume TRUQAP at one lower dose.

FG 251-500 mg/dL Withhold TRUQAP until FG decrease < 160 mg/dL (or < or
FG 14-27.8       8.9 mmol/L) mmol/L
If recovery occurs in < 28 days, resume TRUQAP at one lower dose.
If recovery occurs in > 28 days, permanently.
discontinue TRUQAP.
Adverse Reaction Severity*              TRUQAP Dosage Modification
For life-threatening sequelae of hyperglycemia or if FG
FG > 500 mg/dL or               persists at > 500 mg/dL after 24 hours, permanently
FG > 27.8 mmol/L or               discontinue TRUQAP.
life-threatening sequelae of hyperglycemia at If FG < 500 mg/dL (or < 27.8 mmol/L) within 24 hours, any FG level then follow the guidance in the table for the relevant grade.
Grade 2            Withhold TRUQAP until recovery to < grade 1
Diarrhea [see
If recovery occur in < 28 days, resume TRUQAP at
Warnings and                            same dose or one lower dose as clinically indicated.

Precautions (6.2)]                      If recovery occurs in > 28 days, resume at one lower dose as clinically indicated.
For recurrence, reduce TRUQAP by one lower dose.

Grade 3           Withhold TRUQAP until recovery to < Grade 1. If recovery occurs in < 28 days, resume TRUQAP at same dose or one lower dose as clinically indicated.
If recovery occurs in > 28 days, permanently discontinue TRUQAP.

Grade 4           Permanently discontinue TRUQAP
Withhold TRUQAP until recovery to < Grade 1.
Cutaneous            Grade 2
Resume TRUQAP at the same dose.
Adverse
Persistent or recurrent: reduce TRUQAP by one lower
Reactions dose.
[see Warnings        Grade 3           Withhold TRUQAP until recovery to < Grade 1. If and Precautions recovery occurs in < 28 days, resume TRUQAP at same
(6.3)] dose.
If recovery occurs in > 28 days, resume TRUQAP at one lower dose.
For recurrent Grade 3, permanently discontinue
TRUQAP.
Grade 4           Permanently discontinue TRUQAP
Adverse Reaction Severity*                     TRUQAP Dosage Modification Withhold TRUQAP until recovery to < Grade 1. Resume
Other Adverse         Grade 2
TRUQAP at the same dose.
Reactions
Grade 3              Withhold TRUQAP until recovery to < Grade 1. If
[see Adverse recovery occurs in < 28 days, resume TRUQAP at
Reactions (7.1)] same dose.
If recovery occurs in > 28 days, resume TRUQAP at one lower dose.
Grade 4              Permanently discontinue TRUQAP
*Severity grading according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.


3.5        Dosage Modifications for Strong and Moderate CYP3A Inhibitors Avoid concomitant use with strong CYP3A inhibitors. If concomitant use with a strong CYP3A inhibitor cannot be avoided, reduce the dosage of TRUQAP to 320 mg orally twice daily for 4 days followed by 3 days off [see Drug Interactions (8.1)].


When concomitantly used with a moderate CYP3A inhibitor, reduce the dosage of TRUQAP to 320 mg orally twice daily for 4 days followed by 3 days off. After discontinuation of a strong or moderate CYP3A inhibitor, resume the TRUQAP dosage (after 3 to 5 half-lives of the inhibitor) that was taken prior to initiating the strong or moderate CYP3A inhibitor.


4        DOSAGE FORMS AND STRENGTHS
•       TRUQAP 160 mg: beige film-coated, round, biconvex tablets debossed with ‘CAV’ above ‘160’ on one side and plain on the reverse.
•       TRUQAP 200 mg: beige film-coated, capsule-shaped, biconvex tablets debossed with ‘CAV 200’ on one side and plain on the reverse.