Skip to main content

Rybrevant Injection Dosage

Generic name: Amivantamab 350mg
Dosage form: injection
Drug class: Miscellaneous antineoplastics

Medically reviewed by Drugs.com. Last updated on Jan 24, 2022.

Patient Selection

Select patients for treatment with RYBREVANT based on the presence of EGFR exon 20 insertion mutations [see Clinical Studies (14)]. Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics.

Recommended Dosage

The recommended doses of RYBREVANT, based on baseline body weight, are provided in Table 1, and the dosing schedule is provided in Table 2.

Table 1: Recommended Dose of RYBREVANT Based on Baseline Body Weight
Body Weight at Baseline* Recommended Dose Number of 350 mg/7 mL RYBREVANT Vials
*
Dose adjustments not required for subsequent body weight changes.
Less than 80 kg 1050 mg 3
Greater than or equal to 80 kg 1400 mg 4
Table 2: Dosing schedule for RYBREVANT
Weeks Schedule
Weeks 1 to 4 Weekly (total of 4 doses)
Week 1 - split infusion on Day 1 and Day 2
Weeks 2 to 4 - infusion on Day 1
Week 5 onwards Every 2 weeks starting at Week 5

Administer premedications before each RYBREVANT infusion as recommended [see Dosage and Administration (2.3)]. Administer diluted RYBREVANT intravenously according to the infusion rates in Table 6, with the initial dose as a split infusion on Week 1 on Day 1 and Day 2 [see Dosage and Administration (2.5), (2.6)]. Administer RYBREVANT until disease progression or unacceptable toxicity.

Recommended Premedications

Prior to initial infusion of RYBREVANT (Week 1, Days 1 and 2), administer premedication as described in Table 3 to reduce the risk of infusion-related reactions: [see Warnings and Precautions (5.1)]

Table 3: Premedications
Medication Dose Route of Administration Dosing Window Prior to RYBREVANT Administration
*
Required at all doses.
Required at initial dose (Week 1, Days 1 and 2); optional for subsequent doses.
Antihistamine* Diphenhydramine (25 to 50 mg) or equivalent Intravenous 15 to 30 minutes
Oral 30 to 60 minutes
Antipyretic* Acetaminophen (650 to 1,000 mg) Intravenous 15 to 30 minutes
Oral 30 to 60 minutes
Glucocorticoid Dexamethasone (10 mg) or Methylprednisolone (40 mg) or equivalent Intravenous 45 to 60 minutes

Administer both antihistamine and antipyretic prior to all infusions. Glucocorticoid administration required for Week 1, Days 1 and 2 doses only and as necessary for subsequent infusions.

Dosage Modifications for Adverse Reactions

The recommended RYBREVANT dose reductions for adverse reactions (see Table 5) are listed in Table 4.

Table 4: RYBREVANT Dose Reductions for Adverse Reactions
Body Weight at Baseline Initial Dose 1st Dose Reduction 2nd Dose Reduction 3rd Dose Reduction
Less than 80 kg 1050 mg 700 mg 350 mg Discontinue RYBREVANT
Greater than or equal to 80 kg 1400 mg 1050 mg 700 mg

The recommended RYBREVANT dosage modifications for adverse reactions are provided in Table 5.

Table 5: Recommended RYBREVANT Dosage Modifications for Adverse Reactions
Adverse Reaction Severity Dosage Modifications
Infusion-related reactions (IRR) [see Warnings and Precautions (5.1)] Grade 1 to 2
  • Interrupt RYBREVANT infusion if IRR is suspected and monitor patient until reaction symptoms resolve.
  • Resume the infusion 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 escalated (see Table 6).
  • Include corticosteroid with premedications for subsequent dose (see Table 3).
Grade 3
  • Interrupt RYBREVANT infusion and administer supportive care medications. Monitor patient until reaction symptoms resolve.
  • Resume the infusion 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 escalated (see Table 6).
  • Include corticosteroid with premedications for subsequent dose (see Table 3). For recurrent Grade 3, permanently discontinue RYBREVANT.
Grade 4
  • Permanently discontinue RYBREVANT.
Interstitial Lung Disease (ILD)/pneumonitis [see Warnings and Precautions (5.2)]. Any Grade
  • Withhold RYBREVANT if ILD/pneumonitis is suspected.
  • Permanently discontinue RYBREVANT if ILD/pneumonitis is confirmed.
Dermatologic Adverse Reactions (including dermatitis acneiform, pruritus, dry skin) [see Warnings and Precautions (5.3)] Grade 2
  • Initiate supportive care management.
  • Reassess after 2 weeks; if rash does not improve, consider dose reduction.
Grade 3
  • Withhold RYBREVANT and initiate supportive care management.
  • Upon recovery to ≤ Grade 2, resume RYBREVANT at reduced dose.
  • If no improvement within 2 weeks, permanently discontinue treatment.
Grade 4
  • Permanently discontinue RYBREVANT
Severe bullous, blistering or exfoliating skin conditions (including toxic epidermal necrolysis (TEN)
  • Permanently discontinue RYBREVANT.
Other Adverse Reactions [see Adverse Reactions (6.1)] Grade 3
  • Withhold RYBREVANT until recovery to ≤ Grade 1 or baseline.
  • Resume at the same dose if recovery occurs within 1 week.
  • Resume at reduced dose if recovery occurs after 1 week but within 4 weeks.
  • Permanently discontinue if recovery does not occur within 4 weeks.
Grade 4
  • Withhold RYBREVANT until recovery to ≤Grade 1 or baseline.
  • Resume at reduced dose if recovery occurs within 4 weeks.
  • Permanently discontinue if recovery does not occur within 4 weeks.
  • Permanently discontinue for recurrent Grade 4 reactions.

Preparation

Dilute and prepare RYBREVANT for intravenous infusion before administration.

  • Check that the RYBREVANT solution is colorless to pale yellow. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if discoloration or visible particles are present.
  • Determine the dose required (either 1050 mg or 1400 mg) and number of RYBREVANT vials needed based on patient's baseline weight [see Dosage and Administration (2.2)]. Each vial of RYBREVANT contains 350 mg of amivantamab-vmjw.
  • Withdraw and then discard a volume of either 5% dextrose solution or 0.9% sodium chloride solution from the 250 mL infusion bag equal to the volume of RYBREVANT to be added (i.e., discard 7 mL diluent from the infusion bag for each RYBREVANT vial). Only use infusion bags made of polyvinylchloride (PVC), polypropylene (PP), polyethylene (PE), or polyolefin blend (PP+PE).
  • Withdraw 7 mL of RYBREVANT from each vial and add it to the infusion bag. The final volume in the infusion bag should be 250 mL. Discard any unused portion left in the vial.
  • Gently invert the bag to mix the solution. Do not shake.
  • Diluted solutions should be administered within 10 hours (including infusion time) at room temperature 59°F to 77°F (15°C to 25°C).

Administration

Administer the diluted solution [see Dosage and Administration (2.5)] 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) primed with diluent only. Administration sets must be made of either polyurethane (PU), polybutadiene (PBD) PVC, PP, or PE.

Do not infuse RYBREVANT concomitantly in the same intravenous line with other agents.

Administer RYBREVANT via a peripheral line on Week 1 and Week 2 given the high incidence of infusion-related reactions during initial treatment [see Warnings and Precautions (5.1)]. 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 RYBREVANT infusion intravenously according to the infusion rates in Table 6.

Table 6: Infusion Rates for RYBREVANT Administration
*
Increase the initial infusion rate to the subsequent infusion rate after 2 hours in the absence of infusion-related reactions.
Starting at Week 5, patients are dosed every 2 weeks.
1050 mg Dose
Week Dose
(per 250 mL bag)
Initial Infusion Rate Subsequent Infusion Rate*
Week 1 (split dose infusion)
Week 1 Day 1 350 mg 50 mL/hr 75 mL/hr
Week 1 Day 2 700 mg 50 mL/hr 75 mL/hr
Week 2 1050 mg 85 mL/hr
Week 3 1050 mg 125 mL/hr
Week 4 1050 mg 125 mL/hr
Subsequent weeks 1050 mg 125 mL/hr
1400 mg Dose
Week Dose
(per 250 mL bag)
Initial Infusion Rate Subsequent Infusion Rate*
Week 1 (split dose infusion)
Week 1 Day 1 350 mg 50 mL/hr 75 mL/hr
Week 1 Day 2 1050 mg 35 mL/hr 50 mL/hr
Week 2 1400 mg 65 mL/hr
Week 3 1400 mg 85 mL/hr
Week 4 1400 mg 125 mL/hr
Subsequent weeks 1400 mg 125 mL/hr

Frequently asked questions

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.