In-office dosing and administration
Recommended dosage and pre-infusion medications
Administer RYBREVANT® weekly for 4 weeks, with the initial dose as a split infusion in Week 1 on Day 1 and Day 2, then administer every 2 weeks thereafter, starting at Week 5, until disease progression or unacceptable toxicity1
| 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 |
Recommended Dose of RYBREVANT®
|
Body Weight of Patient at Baseline* |
Recommended Dose |
Number of 350 mg/7 mL RYBREVANT® Vials |
|---|---|---|
| Less than 80 kg | 1050 mg | 3 |
| Greater than or equal to 80 kg | 1400 mg | 4 |
*Dose adjustments not required for subsequent body weight changes.
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.1
| Medication | ||
|---|---|---|
| Dose | Route of Administration | Dosing Window Prior to RYBREVANT® Administration |
| Antihistamine† | ||
| Diphenhydramine (25 to 50 mg) or equivalent | IV | 15 to 30 minutes |
| Oral | 30 to 60 minutes | |
| Antipyretic† | ||
| Acetaminophen (650 to 1,000 mg) | IV | 15 to 30 minutes |
| Oral | 30 to 60 minutes | |
| Glucocorticoid‡ | ||
| Dexamethasone (10 mg) or Methylprednisolone (40 mg) or equivalent | IV | 45 to 60 minutes |
†Required at all doses.
‡Required at initial dose (Week 1, Days 1 and 2); optional for subsequent doses.
Dose modification for adverse reactions
Dose reductions or temporary interruptions may help to manage adverse reactions.
- Permanent discontinuation of RYBREVANT® due to an adverse reaction occurred in 11% of patients. Adverse reactions resulting in permanent discontinuation of RYBREVANT® in ≥1% of patients were pneumonia, IRR, pneumonitis/ILD, dyspnea, pleural effusion, and rash
- Dose interruptions of RYBREVANT® due to an adverse reaction occurred in 78% of patients
- Dose reductions of RYBREVANT® due to an adverse reaction occurred in 15% of patients
| Body Weight at Baseline | |||
|---|---|---|---|
| Initial Dose | 1st Dose Modification | 2nd Dose Modification | 3rd Dose Modification |
| 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 | Discontinue RYBREVANT® |
Preparation and Administration
Preparation of RYBREVANT®
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. 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 of RYBREVANT®
- Administer the diluted solution 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. 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 the table below.
Infusion Rates for RYBREVANT® Administration1
| 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 | ||
§Starting at Week 5, patients are dosed every 2 weeks.
¶Increase the initial infusion rate to the subsequent infusion rate after 2 hours in the absence of infusion-related reactions.
Infusion duration
Clinical trial median infusion times by hours2||
||Based on the safety population (N=302). Recommended phase 2 dose: 1050 mg if baseline weight <80 kg, and 1400 mg if baseline weight ≥80 kg.
ILD, interstitial lung disease; IRR, infusion-related reaction.
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References
1. RYBREVANT® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
2. Data on file. Janssen Biotech, Inc. 2021.