DRUG INTERACTIONS-

1 Effect of VYVGART on Other Drugs-

Concomitant use of VYVGART with medications that bind to the human neonatal Fc receptor (FcRn) (e.g., immunoglobulin products, monoclonal antibodies, or antibody derivates containing the human Fc domain of the IgG subclass) may lower systemic exposures and reduce effectiveness of such medications.

Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor.

When concomitant long-term use of such medications is essential for patient care, consider discontinuing VYVGART and using alternative therapies.

BRIEF SUMMARY

EFGARTIGMUD-(Dec 2021)

Indn-     To treat Generalised Myasthenia Gravis  

Comp-  ­ Injection: 400 mg in 20 mL (20 mg/mL) single-dose vial.  • The recommended dosage is 10 mg/kg administered as an intravenous infusion over one hour once weekly for 4 weeks. In patients weighing 120 kg or more, the recommended dose is 1200 mg per infusion.

CI-  None.

WARNINGS-

­ • Infections: Delay administration of VYVGART to patients with an active infection. Monitor for signs and symptoms of infection in patients treated with VYVGART. If serious infection occurs, administer appropriate treatment and consider withholding VYVGART until the infection has resolved.

• Hypersensitivity Reactions: Angioedema, dyspnea, and rash have occurred. If a hypersensitivity reaction occurs, discontinue the infusion and institute appropriate therapy.

Pat Inform-

Administration of live or live-attenuated vaccines is not recommended during treatment 

 Hypersensitivity Reactions- Inform patients about the signs and symptoms of hypersensitivity reactions. 

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U.S. FDA APPROVED DRUGS SURING 2021                                        

Serial No 49

Name of the Drug-  VYUHART

Active Ingredient -   Efgartigmud- Alfa- fcab

Pharmacological Classification- To treat Generalised Myasthenia Gravis                                                                                                                                                                                                                                                                                                          Date of Approval-      12/17/2021 

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all the information needed to use VYVGART safely and effectively.

See full prescribing information for VYVGART. VYVGART ™ (efgartigimod alfa-fcab) injection, for intravenous use

Initial U.S. Approval: 2021-

INDICATIONS AND USAGE-

­ VYVGART is a neonatal Fc receptor blocker indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

DOSAGE AND ADMINISTRATION-

­ • Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with VYVGART.

 • The recommended dosage is 10 mg/kg administered as an intravenous infusion over one hour once weekly for 4 weeks. In patients weighing 120 kg or more, the recommended dose is 1200 mg per infusion.

 • Administer subsequent treatment cycles based on clinical evaluation; the safety of initiating subsequent cycles sooner than 50 days from the start of the previous treatment cycle has not been established.

 • Must be diluted with 0.9% Sodium Chloride Injection, USP prior to administration.

 • Administer as an intravenous infusion over one hour via a 0.2 micron in-line filter.

DOSAGE FORMS AND STRENGTHS-

­ Injection: 400 mg in 20 mL (20 mg/mL) single-dose vial. 

ADVERSE REACTIONS-

­ Most common adverse reactions ( = 10%) in patients treated with gMG are respiratory tract infections, headache, and urinary tract infection.

CONTRAINDICATIONS-

­ None.

WARNINGS AND PRECAUTIONS-

­ • Infections: Delay administration of VYVGART to patients with an active infection. Monitor for signs and symptoms of infection in patients treated with VYVGART. If serious infection occurs, administer appropriate treatment and consider withholding VYVGART until the infection has resolved.

• Hypersensitivity Reactions: Angioedema, dyspnea, and rash have occurred. If a hypersensitivity reaction occurs, discontinue the infusion and institute appropriate therapy.

DOSAGE AND ADMINISTRATION-

­ • Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with VYVGART.

 • The recommended dosage is 10 mg/kg administered as an intravenous infusion over one hour once weekly for 4 weeks. In patients weighing 120 kg or more, the recommended dose is 1200 mg per infusion.

 • Administer subsequent treatment cycles based on clinical evaluation; the safety of initiating subsequent cycles sooner than 50 days from the start of the previous treatment cycle has not been established.

 • Must be diluted with 0.9% Sodium Chloride Injection, USP prior to administration.

 • Administer as an intravenous infusion over one hour via a 0.2 micron in-line filter.

DOSAGE FORMS AND STRENGTHS-

­ Injection: 400 mg in 20 mL (20 mg/mL) single-dose vial. 

PATIENT COUNSELING INFORMATION-

Infections-

Instruct patients to communicate any history of infections to the healthcare provider and to contact their healthcare provider if they develop any symptoms of an infection.

Advise patients to complete age-appropriate vaccines according to immunization guidelines prior to initiation of a new treatment  cycle with VYVGART.

Administration of live or live-attenuated vaccines is not recommended during treatment with VYVGART

 Hypersensitivity Reactions-

Inform patients about the signs and symptoms of hypersensitivity reactions. Advise patients to contact their healthcare provider immediately for signs or symptoms of hypersensitivity reactions 

Manufactured by: argenx BV Industriepark 7 9052 Zwijnaarde, Belgium Distributed by: argenx US, Inc. 33 Arch Street Boston, MA 02110 License Number 2217 VYVGART is a trademark of argenx BV. © 2021 argenx BV

CLINICAL PHARMACOLOGY-

1. Mechanism of Action-                                                                                         Efgartigimod alfa-fcab is a human IgG1 antibody fragment that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG.

2.Pharmacokinetics-                                                                                                 Efgartigimod alfa-fcab exhibits linear pharmacokinetics, and following single doses of efgartigimod alfa-fcab, exposures increase proportionally up to 50 mg/kg (5 times the recommended dosage).

Distribution-                                                                                                                     The volume of distribution is 15 to 20L.

Metabolism and Elimination-                                                                                  Efgartigimod alfa-fcab is expected to be degraded by proteolytic enzymes into small peptides and amino acids.                                                                                                The terminal half-life is 80 to 120 hours (3 to 5 days). After a single intravenous dose of 10 mg/kg efgartigimod alfa-fcab in healthy subjects, less than 0.1% of the administered dose was recovered in urine.

Specific Populations-                                                                                                 Age, Sex, and Race A population pharmacokinetics analysis assessing the effects of age, sex, and race did not suggest any clinically significant impact of these covariates on efgartigimod alfa-fcab exposures.

Patients with Renal Impairment-                                                                                    No dedicated pharmacokinetic study has been performed in patients with renal impairment.

A population PK analysis of data from the VYVGART clinical studies indicated that patients with mild renal impairment (eGRF 60-89 mL/min/1.72m²) had 22% increase in exposure relative to the exposure in patients with normal renal function

 Patients with Hepatic Impairment-                                                                                No dedicated pharmacokinetic study has been performed in patients with hepatic impairment

 Hepatic impairment -is not expected to affect the pharmacokinetics of efgartigimod alfa-fcab.

Drug Interaction Studies-                                                                                                 Clinical drug interactions studies have not been performed with efgartigimod alfa-fcab. P450 Enzymes Efgartigimod alfa-fcab is not metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

Drug Interactions with Other Drugs or Biological Products-                                    Efgartigimod alfa-fcab may decrease concentrations of compounds that bind to the human FcRn) [see Drug Interactions (7.1)].

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-

 There are no available data on the use of VYVGART during pregnancy. There is no evidence of adverse developmental outcomes following the administration of VYVGART at up to 100 mg/kg/day in rats and rabbits

 The background rate of major birth defects and miscarriage in the indicated population is unknown.

In the U.S. general population, the estimated background rate of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively..

2. Lactation Risk Summary -                                                                                    There is no information regarding the presence of efgartigimod alfa-fcab in human milk, the effects on the breastfed infant, or the effects on milk production. Maternal IgG is known to be present in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VYVGART and any potential adverse effects on the breastfed infant from VYVGART or from the underlying maternal condition

3. Pediatric Use-                                                                                                           Safety and effectiveness in pediatric patients have not been established.

4.Geriatric Use-                                                                                                       Clinical studies of VYVGART did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger adult patients.

5. Renal Impairment-                                                                                                       No dose adjustment of VYVGART is needed for patients with mild renal impairment.

There are insufficient data to evaluate the impact of moderate renal impairment (eGFR 30-59 mL/min/1.73 m²) and severe renal impairment (eGFR <30 mL/min/1.73 m²) on pharmacokinetic parameters of efgartigimod alfa-fcab ].