Posology : מינונים

2           DOSAGE AND ADMINISTRATION

2.1         Recommended Dosage
•   The starting dosage of ZOKINVY for patients with a BSA of 0.39 m2 and above is 115 mg/m2 twice daily with morning and evening meals (see Table 1) to reduce the risk of gastrointestinal adverse reactions [see Adverse Reactions (6.1)]. An appropriate dosage strength of ZOKINVY is not available for patients with a BSA of less than 0.39 m2 [see Indications and Usage (1)].

•   After 4 months of treatment, increase the dosage to 150 mg/m2 twice daily with morning and evening meals (see Table 2).

•   Round all total daily dosages to the nearest 25 mg increment (see Table 1 and Table 2).

•   If a dose is missed, take the dose as soon as possible with food, up to 8 hours prior to the next scheduled dose. If less than 8 hours remains before the next scheduled dose, skip the missed dose, and resume taking ZOKINVY at the next scheduled dose.

Table 1 provides the BSA-based dosage recommendations for the starting dosage of 115 mg/m2 twice daily.

Table 1: Recommended Dosage and Administration for 115 mg/m2 Body Surface Area- Based Dosing
BSA (m2)            Total Daily           Morning Dosing                 Evening Dosing Dosage Rounded        Number of Capsule(s)           Number of Capsule(s) to Nearest 25 mg     ZOKINVY ZOKINVY                ZOKINVY ZOKINVY
50 mg       75 mg              50 mg        75 mg
0.39 - 0.48             100               1                              1 0.49 - 0.59             125                            1                 1 0.6 - 0.7              150                            1                              1 0.71 - 0.81             175               2                                           1 0.82 - 0.92             200               2                              2 0.93 – 1               225               1            1                 2 
Table 2 provides the BSA-based dosage recommendations for the dosage of 150 mg/m2 twice daily.

Table 2: Recommended Dosage and Administration for 150 mg/m2 Body Surface Area-- Based Dosing
BSA (m2)            Total Daily            Morning Dosing                 Evening Dosing Dosage Rounded         Number of Capsule(s)           Number of Capsule(s) to Nearest 25 mg      ZOKINVY ZOKINVY                ZOKINVY ZOKINVY
50 mg       75 mg              50 mg        75 mg
0.39 - 0.45             125                            1                  1 0.46 - 0.54             150                            1                               1 0.55 - 0.62             175                2                                           1 0.63 - 0.7             200                2                              2 0.71 - 0.79             225                1           1                  2 0.8 - 0.87             250                1           1                  1            1 0.88 - 0.95             275                            2                  1            1 0.96 – 1               300                            2                               2 
2.2         Dosage Modifications for Gastrointestinal Adverse Reactions
For patients who have increased their dose of ZOKINVY to 150 mg/m2 twice daily and are experiencing repeated episodes of vomiting and/or diarrhea resulting in dehydration or weight loss, ZOKINVY can be dose reduced to the starting dose of 115 mg/m2 twice daily (see Table 1). Ensure ZOKINVY is taken with the morning and evening meals and with an adequate amount of water.

2.3         Dosage Modifications for Drug Interactions
CYP3A Inhibitors
If concomitant use of ZOKINVY with a weak CYP3A inhibitor is unavoidable [see Warnings and Precautions (5.1), Drug Interactions (7.1)]:
• Reduce to or continue ZOKINVY at the starting dosage of 115 mg/m2 twice daily (see Table 1).
•    Resume the previous ZOKINVY dosage 14 days after discontinuing the concomitant use of the weak CYP3A inhibitor.

2.4              Temporary Discontinuation for Midazolam Use
Temporarily discontinue ZOKINVY for 10 to 14 days before and 2 days after administration of midazolam [see Contraindications (4), Drug Interactions (7.2)].

2.5              Preparation and Administration Instructions
Administer ZOKINVY orally with the morning and evening meals.

Patients Able to Swallow Capsules
• Administer ZOKINVY capsules whole with a sufficient amount of water. Do not chew the capsules.

Patients Unable to Swallow Capsules
• The entire contents of ZOKINVY capsules can be mixed with orange juice or applesauce (see preparation instructions below).
• Do not mix with juice containing grapefruit or Seville oranges [see Contraindications (4), Drug Interactions (7.1)].
• The mixture must be prepared fresh for each dose and taken within approximately 10 minutes of mixing.

Preparation of Dose in Orange Juice
1. For each capsule, empty contents of the capsule into a container containing 5 mL to 10 mL of the liquid.
2. Mix thoroughly with a spoon.
3. Consume entire serving.

Preparation of Dose in Applesauce
1. For each capsule, empty contents of the capsule into a container containing 1 teaspoonful to 2 teaspoonfuls of applesauce.
2. Mix thoroughly with a spoon.
3. Consume entire serving.