DRUG INTERACTIONS-(summary)-

 • 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 RYSTIGGO and using alternate therapies.

DRUG INTERACTIONS-(details)-

1. Effect of RYSTIGGO on Other Drugs-

 Concomitant use of RYSTIGGO with medications that bind to the human neonatal Fc receptor (FcRn) (e.g., immunoglobulin products, monoclonal antibodies, or antibody derivatives 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 RYSTIGGO and using alternative therapies.

BRIEF SUMMARY

ROAZANOLXIZUMAB-(June 2023)

Indication-   To treat generalized myasthenia Gravis in adults who are                                                     anti-acetylcholine receptor or  antimuscle specific tyrosine                                                  kinase antibody positive                       

Dosage-  recommended dosage is subcutaneous infusion once weekly for 6 weeks. Body Weight of Patient Dose Volume to be Infused Less than 50 kg 420 mg 3 mL 50 kg to less than 100 kg 560 mg 4 mL 100 kg and above 840 mg 6 mL

CI-  None

WARNIINGS-  Infections: Delay administration of RYSTIGGO to patients with an active infection. Monitor for signs and symptoms of infection in patients treated   

Pat inform- Instruct patients to communicate any history of infections  and to contact  their healthcare provider if they develop any symptoms of an infection

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U.S. FDA APPROVED  DRUGS DURING 2023

Sr.No-  25

ADVERSE REACTIONS

 The most common adverse reactions (=10%) in patients with gMG are headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea.

WARNINGS AND PRECAUTIONS-

 • Infections: Delay administration of RYSTIGGO to patients with an active infection. Monitor for signs and symptoms of infection in patients treated with RYSTIGGO.

If serious infection occurs, administer appropriate treatment and consider withholding RYSTIGGO until the infection has resolved.

 • Aseptic Meningitis: Serious events of aseptic meningitis have been reported. Monitor for symptoms; diagnostic workup and treatment should be initiated according to the standard of care.

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

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

Vaccinations-

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

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

 Aseptic Meningitis-

 Inform patients that RYSTIGGO could cause aseptic meningitis.

Instruct patients to contact their healthcare provider if symptoms consistent with meningitis develop.

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: UCB, Inc. 1950 Lake Park Drive Smyrna, GA 30080 US License Number 1736 RYSTIGGO® is a registered trademark of the UCB Group of Companies. ©2023 UCB, Inc., Smyrna, GA 30080. All rights reserved.

CLINICAL PHARMACOLOGY

1. Mechanism of Action-

Rozanolixizumab-noli is a humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG. Reference ID: 5197660

2. Pharmacodynamics-

In Study 1], the pharmacological effect of rozanolixizumab-noli was assessed by measuring the decrease in serum IgG levels and AChR and MuSK autoantibody levels. In patients testing positive for AChR and MuSK autoantibodies who were treated with RYSTIGGO, there was a reduction in total IgG levels relative to baseline.

Decreases in AChR autoantibody and MuSK autoantibody levels followed a similar pattern.

3. Pharmacokinetics-

Rozanolixizumab-noli exhibited nonlinear pharmacokinetics. Rozanolixizumab-noli exposure increased in a greater than dose-proportional manner over a dose range from 1 mg/kg to 20 mg/kg (two times the maximum recommended dose) following subcutaneous administration.

Absorption-

Following subcutaneous administration of rozanolixizumab-noli, peak plasma levels were achieved after approximately 2 days in healthy subjects.

Distribution-

The apparent volume of distribution of rozanolixizumab-noli is 6.6 L.

Elimination-

Metabolism-

Rozanolixizumab-noli is expected to be degraded by proteolytic enzymes into small peptides and amino acids.

Excretion -T

he apparent clearance for the rozanolixizumab-noli is 0.89 L/day.

Specific Populations-

Age, Sex, and Race The pharmacokinetics of rozanolixizumab-noli were not affected by age, sex, or race based on a population pharmacokinetics analysis.

Patients with Renal Impairment-

No dedicated pharmacokinetic study has been conducted in patients with renal impairment.

Renal impairment is not expected to affect the pharmacokinetics of rozanolixizumab-noli.

Based on a population pharmacokinetic analysis, which included participants with mild to moderate renal impairment, renal function (estimated glomerular filtration rate [eGFR] 38–161 mL/min/1.73 m2) had no clinically significant effect on rozanolixizumab-noli apparent clearance.

No dose adjustment is required in patients with renal impairment.

Patients with Hepatic Impairment-

No dedicated pharmacokinetic study has been conducted in patients with hepatic impairment.

Hepatic impairment is not expected to affect the pharmacokinetics of rozanolixizumab-noli.

Drug Interaction Studies-

 Clinical drug interaction studies have not been performed with rozanolixizumab-noli.

P450 Enzymes Rozanolixizumab-noli is not metabolized by cytochrome P450 enzymes. Interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

Drug Interactions with Other Drugs or Biological Products Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn .

6. Immunogenicity-

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay.

Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of rozanolixizumab-noli or of other rozanolixizumab products.

 USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-

 There are limited data on RYSTIGGO use in pregnant women to inform a drugassociated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

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

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

2. Lactation Risk Summary-

 There are no data on the presence of rozanolixizumab-noli 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 RYSTIGGO and any potential adverse effects on the breastfed child from RYSTIGGO 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 RYSTIGGO did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger adult patients.