Rybrevant Dosage/Direction for Use

Important Dosage Information: Administer premedications before each RYBREVANT infusion as recommended [see Recommended Premedications as follows].
Administer diluted RYBREVANT intravenously according to the infusion rates in Tables 11 and 12, with the initial dose as a split infusion on Week 1 on Day 1 and Day 2 [see Administration as follows].
Administer RYBREVANT via peripheral line for Week 1 Day 1 and 2 and Week 2 to reduce the risk of infusion-related reactions [see Administration as follows].
When administering RYBREVANT in combination with carboplatin and pemetrexed, infuse pemetrexed first, carboplatin second, and RYBREVANT last [see Administration as follows].
Patient Selection: Select patients for treatment with RYBREVANT based on the presence of a mutation as detected by a validated test. (See Table 4.)

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Recommended Dosage of RYBREVANT in Combination with Carboplatin and Pemetrexed for the Treatment of NSCLC - Every 3-week dosing: The recommended dosage of RYBREVANT, administered in combination with carboplatin and pemetrexed is based on baseline body weight is provided in Table 5. (See Table 5.)

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The recommended order of administration and regimen for RYBREVANT in combination with carboplatin and pemetrexed are provided in Table 6. (See Table 6.)

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Recommended Dosage of RYBREVANT as a Single Agent - Every 2-week dosing: The recommended dosage of RYBREVANT as a single agent, based on baseline body weight, are provided in Table 7. Administer RYBREVANT until disease progression or unacceptable toxicity. (See Table 7.)

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Recommended Premedications: Prior to the initial infusion of RYBREVANT (Week 1, Day 1 and 2), administer premedications as described in Table 8 to reduce the risk of infusion-related reactions [see Infusion-Related Reactions under Precautions]. (See Table 8.)
Glucocorticoid administration is required for Week 1, Day 1 and 2 dose only and upon re-initiation after prolonged dose interruptions, then as necessary for subsequent infusions (see Table 8). Administer both antihistamine and antipyretic prior to all infusions.

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Dosage Modifications for Adverse Reactions: The recommended dose reductions for adverse reactions for RYBREVANT are listed in Table 9. (See Table 9.)

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The recommended dosage modifications and management for adverse reactions for RYBREVANT are provided in Table 10. (See Table 10.)

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Recommended Dosage Modifications for Adverse Reactions for RYBREVANT in Combination with Carboplatin and Pemetrexed: When administering RYBREVANT in combination with carboplatin and pemetrexed, modify the dosage of one or more drugs. Withhold or discontinue RYBREVANT as shown in Table 10. Refer to prescribing information for carboplatin and pemetrexed for additional dosage modification information.
Administration: Administer the diluted RYBREVANT solution [see Preparation under Cautions for Usage] by intravenous infusion using an infusion set fitted with a flow regulator and with an in-line, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.2 micrometer).
Administration sets must be made of either polyurethane (PU), polybutadiene (PBD), PVC, PP, or PE.
The administration set with filter, must be primed with either 5% Dextrose Injection or 0.9% Sodium Chloride Injection prior to the initiation of each RYBREVANT infusion.
Do not infuse RYBREVANT concomitantly in the same intravenous line with other agents.
RYBREVANT in Combination with Carboplatin and Pemetrexed: Administer RYBREVANT in combination with carboplatin and pemetrexed infusions every 3 weeks intravenously until disease progression or unacceptable toxicity according to the infusion rates in Table 11. (See Table 11.)
Administer RYBREVANT via a peripheral line on Week 1 and Week 2 to reduce the risk of infusion-related reactions during initial treatment [see Infusion-Related Reactions under Precautions].
RYBREVANT may be administered via central line for subsequent weeks.
For the initial infusion, prepare RYBREVANT as close to administration time as possible to allow for the possibility of extended infusion time in the event of an infusion-related reaction.
Administer the pemetrexed infusion first, carboplatin infusion second, and the RYBREVANT infusion last.

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RYBREVANT as a Single Agent: Administer RYBREVANT as a single agent infusion every 2 weeks intravenously until disease progression or unacceptable toxicity according to the infusion rates in Table 12. (See Table 12.)
Administer RYBREVANT via a peripheral line on Week 1 and Week 2, to reduce the risk of infusion-related reactions during initial treatment [see Infusion-Related Reactions under Precautions].
RYBREVANT may be administered via central line for subsequent weeks.
For the initial infusion, prepare RYBREVANT as close to administration time as possible to allow for the possibility of extended infusion time in the event of an infusion-related reaction.

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