Usual Adult Dose for Non-Small Cell Lung Cancer

Weeks 1 to 4:

• Less than 80 kg: 1050 mg IV once a week for 4 doses
• At least 80 kg: 1400 mg IV once a week for 4 doses

• Less than 80 kg: 1050 mg IV every 2 weeks
• At least 80 kg: 1400 mg IV every 2 weeks

• Week 1 (split dose infusion):
• Day 1 (350 mg dose):
• Initial rate: 50 mL/hour
• Subsequent rate: 75 mL/hour
• Day 2 (700 mg dose):
• Initial rate: 50 mL/hour
• Subsequent rate: 75 mL/hour
• Week 2 (1050 mg dose): 85 mL/hour
• Subsequent weeks (1050 mg dose): 125 mL/hour

• Week 1 (split dose infusion):
• Day 1 (350 mg dose):
• Initial rate: 50 mL/hour
• Subsequent rate: 75 mL/hour
• Day 2 (1050 mg dose):
• Initial rate: 35 mL/hour
• Subsequent rate: 50 mL/hour
• Week 2 (1400 mg dose): 65 mL/hour
• Week 3 (1400 mg dose): 85 mL/hour
• Subsequent weeks (1400 mg dose): 125 mL/hour

• The dose should be based on baseline body weight; dose adjustments are not needed for subsequent body weight changes.
• The initial dose should be administered as a split infusion in Week 1, on Day 1 and Day 2.
• Before the initial infusion on Week 1 (Days 1 and 2), premedication should be administered to reduce the risk of infusion-related reactions.
• An antihistamine and antipyretic should be administered before all infusions.
• A glucocorticoid is required for Week 1 (Days 1 and 2) doses only and should be used as needed for subsequent infusions.
• The initial infusion rate may be increased to the subsequent infusion rate after 2 hours without an infusion-related reaction.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Dose reductions for adverse reactions:

• Less than 80 kg:
• First dose reduction: 700 mg
• Second dose reduction: 350 mg
• Third dose modification: This drug should be discontinued.
• At least 80 kg:
• First dose reduction: 1050 mg
• Second dose reduction: 700 mg
• Third dose modification: This drug should be discontinued.

• Grade 2: Supportive care management should be started. Reactions should be reassessed after 2 weeks; if rash does not improve, dose reduction should be considered.
• Grade 3: This drug should be withheld and supportive care management should be started. Upon recovery to Grade 2 or less, this drug should resume at a reduced dose; if no improvement within 2 weeks, this drug should be permanently discontinued.
• Grade 4 and severe bullous, blistering, or exfoliating skin conditions (including toxic epidermal necrolysis): This drug should be permanently discontinued.

• Grade 1 to 2: The infusion should be interrupted if infusion-related reaction is suspected; the patient should be monitored until reaction symptoms resolve. The infusion should resume at 50% of the infusion rate at which the reaction occurred; if there are no additional symptoms after 30 minutes, the infusion rate may be increased according to the recommended infusion rate. A corticosteroid should be included with premedications for the next dose.
• Grade 3: The infusion should be interrupted and supportive care agents should be administered; the patient should be monitored until reaction symptoms resolve. The infusion should resume at 50% of the infusion rate at which the reaction occurred; if there are no additional symptoms after 30 minutes, the infusion rate may be increased according to the recommended infusion rate. A corticosteroid should be included with premedications for the next dose.
• Recurrent Grade 3 or Grade 4: This drug should be permanently discontinued.

• Any Grade: This drug should be withheld if ILD/pneumonitis is suspected; this drug should be permanently discontinued if ILD/pneumonitis is confirmed.

• Grade 3: This drug should be withheld until recovery to Grade 1 or less or baseline. If recovery occurs within 7 days, this drug should resume at the same dose; if recovery occurs after 7 days (but within 4 weeks), this drug should resume at a reduced dose. If recovery does not occur within 4 weeks, this drug should be permanently discontinued.
• Grade 4: This drug should be withheld until recovery to Grade 1 or less or baseline. If recovery occurs within 4 weeks, this drug should resume at a reduced dose; this drug should be permanently discontinued if recovery does not occur within 4 weeks or for recurrent Grade 4 reactions.

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Select patients for treatment based on the presence of EGFR exon 20 insertion mutations; for information on US FDA-approved tests: http://www.fda.gov/CompanionDiagnostics
• Administer premedication to reduce the risk of infusion-related reactions; premedications include:
• Antihistamine (diphenhydramine [25 to 50 mg] or equivalent): Administer 15 to 30 minutes (IV) or 30 to 60 minutes (oral) before administration of this drug; required at all doses.
• Antipyretic (acetaminophen [650 to 1000 mg]): Administer 15 to 30 minutes (IV) or 30 to 60 minutes (oral) before administration of this drug; required at all doses.
• Glucocorticoid (dexamethasone [10 mg] or methylprednisolone [40 mg] or equivalent): Administer IV 45 to 60 minutes before administration of this drug; required at initial dose (Week 1, Days 1 and 2) but optional for subsequent doses.
• Administer the diluted solution by IV infusion using an infusion set fitted with a flow regulator and with an in-line, sterile, nonpyrogenic, low protein-binding polyethersulfone (PES) filter (pore size: 0.2 micrometer) primed with diluent only.
• Administration sets must be made of either polyurethane (PU), polybutadiene (PBD), polyvinylchloride (PVC), polypropylene (PP), or polyethylene (PE).
• Due to the high incidence of infusion-related reactions during initial therapy, infuse this drug via a peripheral line for Weeks 1 and 2; infusions may be administered via central line for subsequent weeks.
• Do not infuse this drug concomitantly in the same IV line with other agents.

• Unopened vials: Store in a refrigerator at 2C to 8C (36F to 46F) in original carton to protect from light; do not freeze.
• Diluted solutions: Administer within 10 hours (including infusion time) at room temperature 15C to 25C (59F to 77F).

• This drug should be diluted and prepared for IV infusion before administration; infusion bags must be made of PVC, PP, PE, or polyolefin blend (PP+PE).
• The initial infusion should be prepared as close to administration time as possible to allow for a possibly extended infusion time in case of an infusion-related reaction.
• The manufacturer product information should be consulted.

• Compatible: 5% dextrose solution, 0.9% sodium chloride solution

• This indication was approved under accelerated approval based on overall response rate and duration of response; continued approval may depend on verification and description of clinical benefit in confirmatory trials.

• General: For any signs/symptoms of infusion reactions (during infusion)
• Respiratory: For new/worsening symptoms indicative of ILD/pneumonitis (during therapy)

• Read the US FDA-approved patient labeling (Patient Information).
• Notify health care provider immediately if any signs/symptoms of infusion-related reactions occur.
• Contact health care provider immediately for new/worsening respiratory symptoms.
• Limit direct sun exposure during therapy and for 2 months after the last dose; use broad-spectrum ultraviolet A (UVA)/ultraviolet B (UVB) sunscreen and wear protective clothing during therapy. Apply alcohol-free emollient cream to dry skin.
• Contact ophthalmologist if eye symptoms develop; contact lenses should be discontinued until symptoms are evaluated.
• Contact health care provider for signs/symptoms of paronychia.
• Patients of childbearing potential: Use effective contraception during therapy and for 3 months after the last dose; notify health care provider of a known/suspected pregnancy.
• Do not breastfeed during therapy and for 3 months after the last dose.

Frequently asked questions

• How does Rybrevant work?
• How is Rybrevant administered?