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Introduction

Efgartigimod alfa, a neonatal Fc receptor blocker, is an immunomodulatory agent.

Efgartigimod alfa and hyaluronidase-qvfc is a fixed combination of efgartigimod alfa (a neonatal Fc receptor blocker) and hyaluronidase (an endoglycosidase).

Uses for Efgartigimod Alfa (Systemic)

Myasthenia Gravis

Treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) antibody positive (designated an orphan drug by FDA for this use).

Immunosuppressive therapies, including efgartigimod alfa, are typically considered for patients with myasthenia gravis symptoms not controlled by symptomatic therapy alone; some experts suggest that efgartigimod alfa may be used for third-line or later immunosuppressive therapy in myasthenia gravis.

Efgartigimod Alfa (Systemic) Dosage and Administration

General

Pretreatment Screening

• Evaluate the need for age-appropriate vaccinations based on immunization guidelines prior to initiating a new treatment cycle with efgartigimod alfa-containing products.

Patient Monitoring

• Monitor for clinical signs and symptoms of hypersensitivity reaction during administration of efgartigimod alfa-containing products. Continue to monitor for at least 30 minutes after administration of efgartigimod alfa/hyaluronidase-qvfc and for 1 hour after administration of efgartigimod alfa-fcab.

• Monitor closely for reduced efficacy of drugs that bind to the human neonatal F_c receptor if used concomitantly with efgartigimod alfa-containing products.

• Monitor for signs and symptoms of infection in patients who receive efgartigimod alfa-containing products.

Administration

Administration

Efgartigimod alfa-fcab (Vyvgart) is administered by IV infusion, after dilution; available as a 20 mg/mL (400 mg) single-dose vial.

The fixed combination of efgartigimod alfa and hyaluronidase-qvfc (efgartigimod alfa/hyaluronidase-qvfc; Vyvgart Hytrulo) is administered by sub-Q injection; available as a single-dose vial that contains 1008 mg of efgartigimod alfa and 11,200 units of hyaluronidase per 5.6 mL (180 mg/2000 units per mL).

If a scheduled dose is missed, administer the missed dose for up to 3 days after the scheduled time, and resume original schedule until complete.

IV Administration

Efgartigimod alfa-fcab (Vyvgart) is administered as an IV infusion through an IV line containing a sterile, in-line, 0.2 micron filter. Administer the diluted solution using polyethylene (PE), polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), or ethylene/polypropylene copolymer (polyolefin) bags with PE, PVC, EVA, or polyurethane/polypropylene infusion lines. After administration, flush the entire IV line with 0.9% sodium chloride for injection. Other drugs should not be mixed with efgartigimod alfa-fcab or injected into infusion side ports.

Dilution

After calculating the total dose (mg) required using the patient's body weight, withdraw dose from vial(s) using a sterile syringe and needle, then dilute the withdrawn dose with 0.9% sodium chloride to yield a total infusion volume of 125 mL. Mix the diluted solution using gentle inversion; do not shake.

Rate of Administration

Administer the total infusion volume of 125 mL over 1 hour.

Sub-Q Administration

Efgartigimod alfa/hyaluronidase-qvfc (VyvgartHytrulo) is administered via sub-Q injection using a winged infusion set without dilution. Do not administer IV.

To prepare, remove vial from refrigeration at least 15 minutes prior to administration and allow to come to room temperature; do not use external heat sources. Withdraw entire contents from vial using a polypropylene syringe and 18 gauge stainless steel transfer needle, removing large air bubbles if present. Administer immediately after preparation as the product does not contain preservatives.

Administer using a winged infusion set made of PVC, 25 gauge, 12 inch tubing, with a maximum priming volume of 0.4 mL. Remove transfer needle from syringe and connect syringe to the winged infusion set. Before administering, fill tubing of the winged infusion set by gently pressing the syringe plunger until it reaches 5.6 mL; there should be solution at the end of the winged infusion set needle.

Inject into the abdomen, at least 2–3 inches from the navel. Inject sub-Q into pinched skin at a 45 degree angle over 30–90 seconds; do not inject into red, bruised, tender, or hard areas or into areas with moles or scars. Rotate injection sites for subsequent injections.

Dosage

Adults

Generalized Myasthenia Gravis

IV Infusion - Efgartigimod alfa-fcab (Vyvgart)

10 mg/kg given as an IV infusion over 1 hour once weekly for 4 weeks. In adults weighing ≥120 kg, the recommended dosage is 1200 mg (3 vials) per infusion.

Administer subsequent treatment cycles based on clinical evaluation; safety of administration <50 days from the start of previous treatment cycle not established.

Sub-Q Injection - Efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo)

1008 mg efgartigimod alfa/11,200 units hyaluronidase administered sub-Q over approximately 30 to 90 seconds once weekly for 4 weeks.

Administer subsequent treatment cycles based on clinical evaluation; safety of administration <50 days from the start of previous treatment cycle not established.

Prescribing Limits

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No dosage adjustment necessary in mild (eGFR ≥60 mL/minute/1.73 m²) renal impairment.

No specific dosage adjustments in moderate (eGFR 30–59 mL/minute/1.73m²) and severe (eGFR <30 mL/minute/1.73 m²) renal impairment.

Geriatric Use

No specific dosage recommendations at this time.

Contraindications

• None.

Warnings/Precautions

Infections

May increase risk of infection. Delay administration of efgartigimod alfa-containing products until resolution of active infection. Monitor for clinical signs and symptoms of infection during treatment. If serious infection occurs, administer appropriate treatment and consider withholding treatment until infection resolution.

Immunizations

Immunization during treatment not studied. Safety and response to immunization with live or live attenuated vaccines not known. Vaccination with live or live attenuated vaccines not recommended during treatment. Evaluate need for age-appropriate vaccination before initiating a new treatment cycle with efgartigimod alfa-containing products.

Hypersensitivity Reactions

Hypersensitivity reactions, such as rash, angioedema, and dyspnea observed with efgartigimod alfa-fcab. Monitor for signs and symptoms of hypersensitivity reactions during and for 30 minutes (for efgartigimod alfa/hyaluronidase-qvfc) to 1 hour (for efgartigimod alfa-fcab) post-administration. Discontinue IV administration of efgartigimod alfa-fcab.⁽¹⁾ Institute appropriate supportive care if a hypersensitivity reaction occurs during administration.

Specific Populations

Pregnancy

No evidence available on use of efgartigimod alfa-containing products in pregnancy. No evidence of adverse developmental outcomes in animal studies with doses up to 100 mg/kg/day. Since monoclonal antibodies increasingly cross the placenta as pregnancy progresses, efgartigimod alfa may be transmitted to the developing fetus.

Efgartigimod alfa expected to reduce maternal IgG antibody levels; therefore, reduction in passive protection to newborn anticipated. Consider risk and benefits prior to administration of live or live attenuated vaccines to infants exposed to efgartigimod alfa in utero.

Lactation

Not known whether efgartigimod alfa or hyaluronidase distribute into milk, affect milk production, or affect breastfed infants. Maternal IgG is present in human milk. Consider benefits of breastfeeding, the clinical well-being of the mother, and any potential adverse effects on the infant.⁽¹⁾⁽⁶⁾

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

Clinical studies did not include sufficient numbers of patients ≥65 years of age to assess differences in response compared to younger adults.

Hepatic Impairment

No dedicated study conducted in patients with hepatic impairment. Pharmacokinetics of efgartigimod alfa not expected to be altered by hepatic impairment.

Renal Impairment

No dedicated study conducted in patients with renal impairment. A population pharmacokinetic analysis found a 22% and 11% increase in exposure to efgartigimod alfa-fcab and efgartigimod alfa and hyaluronidase-qvfc, respectively, in patients with mild renal impairment (eGFR 60-89 mL/min per 1.73 m²) compared to those with normal renal function. Insufficient data available to evaluate the impact of moderate (eGFR 30–59 mL/min per 1.73 m²) and severe (eGFR <30 mL/min per 1.73 m²) renal impairment on efgartigimod alfa pharmacokinetics.

Common Adverse Effects

Common adverse reactions (≥10%) in patients receiving efgartigimod alfa-fcab: respiratory tract infections, headache, urinary tract infection. Injection site reactions are also common in patients receiving efgartigimod alfa/hyaluronidase-qvfc.

General

Pretreatment Screening

• Evaluate the need for age-appropriate vaccinations based on immunization guidelines prior to initiating a new treatment cycle with efgartigimod alfa-containing products.

Patient Monitoring

• Monitor for clinical signs and symptoms of hypersensitivity reaction during administration of efgartigimod alfa-containing products. Continue to monitor for at least 30 minutes after administration of efgartigimod alfa/hyaluronidase-qvfc and for 1 hour after administration of efgartigimod alfa-fcab.

• Monitor closely for reduced efficacy of drugs that bind to the human neonatal F_c receptor if used concomitantly with efgartigimod alfa-containing products.

• Monitor for signs and symptoms of infection in patients who receive efgartigimod alfa-containing products.

Administration

Administration

Efgartigimod alfa-fcab (Vyvgart) is administered by IV infusion, after dilution; available as a 20 mg/mL (400 mg) single-dose vial.

The fixed combination of efgartigimod alfa and hyaluronidase-qvfc (efgartigimod alfa/hyaluronidase-qvfc; Vyvgart Hytrulo) is administered by sub-Q injection; available as a single-dose vial that contains 1008 mg of efgartigimod alfa and 11,200 units of hyaluronidase per 5.6 mL (180 mg/2000 units per mL).

If a scheduled dose is missed, administer the missed dose for up to 3 days after the scheduled time, and resume original schedule until complete.

IV Administration

Efgartigimod alfa-fcab (Vyvgart) is administered as an IV infusion through an IV line containing a sterile, in-line, 0.2 micron filter. Administer the diluted solution using polyethylene (PE), polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), or ethylene/polypropylene copolymer (polyolefin) bags with PE, PVC, EVA, or polyurethane/polypropylene infusion lines. After administration, flush the entire IV line with 0.9% sodium chloride for injection. Other drugs should not be mixed with efgartigimod alfa-fcab or injected into infusion side ports.

Dilution

After calculating the total dose (mg) required using the patient's body weight, withdraw dose from vial(s) using a sterile syringe and needle, then dilute the withdrawn dose with 0.9% sodium chloride to yield a total infusion volume of 125 mL. Mix the diluted solution using gentle inversion; do not shake.

Rate of Administration

Administer the total infusion volume of 125 mL over 1 hour.

Sub-Q Administration

Efgartigimod alfa/hyaluronidase-qvfc (VyvgartHytrulo) is administered via sub-Q injection using a winged infusion set without dilution. Do not administer IV.

To prepare, remove vial from refrigeration at least 15 minutes prior to administration and allow to come to room temperature; do not use external heat sources. Withdraw entire contents from vial using a polypropylene syringe and 18 gauge stainless steel transfer needle, removing large air bubbles if present. Administer immediately after preparation as the product does not contain preservatives.

Administer using a winged infusion set made of PVC, 25 gauge, 12 inch tubing, with a maximum priming volume of 0.4 mL. Remove transfer needle from syringe and connect syringe to the winged infusion set. Before administering, fill tubing of the winged infusion set by gently pressing the syringe plunger until it reaches 5.6 mL; there should be solution at the end of the winged infusion set needle.

Inject into the abdomen, at least 2–3 inches from the navel. Inject sub-Q into pinched skin at a 45 degree angle over 30–90 seconds; do not inject into red, bruised, tender, or hard areas or into areas with moles or scars. Rotate injection sites for subsequent injections.

Dosage

Adults

Generalized Myasthenia Gravis

IV Infusion - Efgartigimod alfa-fcab (Vyvgart)

10 mg/kg given as an IV infusion over 1 hour once weekly for 4 weeks. In adults weighing ≥120 kg, the recommended dosage is 1200 mg (3 vials) per infusion.

Administer subsequent treatment cycles based on clinical evaluation; safety of administration <50 days from the start of previous treatment cycle not established.

Sub-Q Injection - Efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo)

1008 mg efgartigimod alfa/11,200 units hyaluronidase administered sub-Q over approximately 30 to 90 seconds once weekly for 4 weeks.

Administer subsequent treatment cycles based on clinical evaluation; safety of administration <50 days from the start of previous treatment cycle not established.

Prescribing Limits

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No dosage adjustment necessary in mild (eGFR ≥60 mL/minute/1.73 m²) renal impairment.

No specific dosage adjustments in moderate (eGFR 30–59 mL/minute/1.73m²) and severe (eGFR <30 mL/minute/1.73 m²) renal impairment.

Geriatric Use

No specific dosage recommendations at this time.

No formal drug interaction studies conducted to date. Not metabolized by CYP enzymes; therefore, interactions with medications that are substrates, inhibitors, or inducers of CYP enzymes not expected.

Drug Interaction Potential

When efgartigimod alfa is used concomitantly with other drugs that bind to the human neonatal Fc receptor (FcRn) (e.g., immunoglobulin products, monoclonal antibodies, antibody derivatives that contain the human Fc domain of the IgG subclass), systemic exposure and efficacy of such medications may be decreased. Monitor for reduced efficacy of drugs that bind to FcRn when used concomitantly with efgartigimod alfa-containing products. When the long-term concomitant use of these drugs is necessary, consider discontinuance of efgartigimod alfa-containing products and use of an alternative treatment.

Vaccines

Due to the propensity of efgartigimod alfa-fcab to cause transient reductions in circulating immunoglobulin G (IgG), immunization with live or live-attenuated vaccines is not recommended during treatment. Evaluate the need for age-appropriate vaccinations prior to initiating a new treatment cycle with efgartigimod alfa-containing products.