DRUG INTERACTIONS-

No formal drug interaction studies have been conducted.

BRIEF SUMMARY

ANIFROLUMAB-fnia- (July 2021)

Indn- To treat moderate to- severe lupus eryhthematous  along with standard therapy                                                                                                                                    

ADR- Most common adverse reactions) are liver test abnormalities, diarrhea, abdominal pain, vomiting, and fat-soluble vitamin deficiency.

CI-   is contraindicated in patients with a history of anaphylaxis with anifrolumab-fnia. 

WARNINGS-

­ • Liver Test Abnormalities: Obtain baseline liver tests and monitor during treatment. Dose reduction or treatment interruption may be required if abnormalities occur. 

 • Diarrhea: Treat dehydration. Treatment interruption or discontinuation may be required for persistent diarrhea.

Pat Inform-

Serious Infections-  Inform patients that SAPHNELO may decrease their ability to fight infections, and that serious infections, including fatal ones, occurred in patients receiving  in clinical trials.

Also inform patients that they are at increased risk of respiratory infections and herpes zoster during treatment 

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U.S. FDA APPROVED DRUGS SURING 2021                                          

Serial No 33

Name of the Drug-    SAPHNELO

Active Ingredient -   Anifrolumab-fnia

Pharmacological Classification- To treat moderate to- severe lupus eryhthematous  along with standard therapy                                                                                                                                                                                                

 Date of Approval-          7/30/2021

HIGHLIGHTS OF PRESCRIBING INFORMATION-

 WARNINGS AND PRECAUTIONS-

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

See full prescribing information for SAPHNELO. SAPHNELO (anifrolumab-fnia) injection, for intravenous use

Initial U.S. Approval: 2021

 INDICATIONS AND USAGE-

­ SAPHNELO is a type I interferon (IFN) receptor antagonist indicated for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE), who are receiving standard therapy.

 Limitations of Use: The efficacy of SAPHNELO has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Use of SAPHNELO is not recommended in these situations.

ADVERSE REACTIONS-

­ Most common adverse reactions (>2%) are liver test abnormalities, diarrhea, abdominal pain, vomiting, and fat-soluble vitamin deficiency.

 CONTRAINDICATIONS-

­ SAPHNELO is contraindicated in patients with a history of anaphylaxis with anifrolumab-fnia. 

WARNINGS AND PRECAUTIONS-

­ • Liver Test Abnormalities: Obtain baseline liver tests and monitor during treatment. Dose reduction or treatment interruption may be required if abnormalities occur. Fo

 • Diarrhea: Treat dehydration. Treatment interruption or discontinuation may be required for persistent diarrhea.

 • Fat-Soluble Vitamin (FSV) Deficiency: Obtain baseline levels and monitor during treatment. Supplement if deficiency is observed. If FSV deficiency persists or worsens despite FSV supplementation, discontinue treatment.

 DOSAGE AND ADMINISTRATION-

­ The recommended dosage is 300 mg as an intravenous infusion over a 30-minute period every 4 weeks. For complete dilution and intravenous administration instructions see Full Prescribing Information.

 DOSAGE FORMS AND STRENGTHS-

­ Injection: 300 mg/2 mL (150 mg/mL) in a single-dose vial.

PATIENT COUNSELING INFORMATION-

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Serious Infections-                                                                                                            Inform patients that SAPHNELO may decrease their ability to fight infections, and that serious infections, including fatal ones, occurred in patients receiving SAPHNELO in clinical trials.

Also inform patients that they are at increased risk of respiratory infections and herpes zoster during treatment with SAPHNELO 

Advise patients to contact their healthcare provider if they develop any symptoms of an infection, including fever or flu-like symptoms; muscle aches; cough; shortness of breath; burning when they urinate or urinating more often than usual; diarrhea or stomach pain; shingles (a red skin rash that can cause pain and burning).

Hypersensitivity Reactions/Anaphylaxis-                                                                        Inform patients that serious hypersensitivity reactions, including anaphylaxis, have been reported in patients who received SAPHNELO.

Instruct patients to immediately tell their healthcare provider or go to the emergency department of their nearest hospital, if they experience symptoms of an allergic reaction (e.g., anaphylaxis) during or after the administration of SAPHNELO

 Symptoms may include swelling of the face, tongue, or mouth, breathing difficulties, and/or fainting, dizziness, feeling lightheaded (due to a drop in blood pressure). Immunizations Inform patients that they should not receive live or live-attenuated vaccines while receiving SAPHNELO.

Advise patients to discuss with their healthcare provider before seeking immunizations on their own 

Pregnancy-                                                                                                                   Advise female patients to inform their healthcare provider if they intend to become pregnant during therapy, suspect they are pregnant or become pregnant while receiving SAPHNELO 

Manufactured by: AstraZeneca AB Södertälje, Sweden SE-15185 US License No. 2059 Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850 ©AstraZeneca 2021

CLINICAL PHARMACOLOGY

1. Mechanism of Action-     

 Anifrolumab-fnia is a human IgG1? monoclonal antibody that binds to subunit 1 of the type I interferon receptor (IFNAR) with high specificity and affinity.

This binding inhibits type I IFN signaling, thereby blocking the biologic activity of 7 Reference ID: 4834399 type I IFNs. Anifrolumab-fnia also induces the internalization of IFNAR1, thereby reducing the levels of cell surface IFNAR1 available for receptor assembly.

2. Pharmacodynamics-                                                                                                    In patients with SLE, following the administration of anifrolumab-fnia at 300 mg dose, via intravenous infusion every 4 weeks for 52 weeks, neutralization (=80%) of a type I IFN gene signature was observed from Week 4 to Week 52 in blood samples of patients with elevated levels of type I IFN inducible genes and returned to baseline levels within 8 to 12 weeks following withdrawal of anifrolumab-fnia at the end of the 52-week treatment period.

3. Pharmacokinetics-                                                                                                    The PK of anifrolumab-fnia was studied in adult patients with SLE following intravenous doses ranging from 100 to 1000 mg once every 4 weeks, and healthy volunteers following a single intravenous dose at 300 mg.

Distribution-                                                                                                                      Based on population PK analysis, the estimated volume of distribution at steady state for a typical patient with SLE (69.1 kg) is 6.23 L.

Elimination-                                                                                                                  From population PK analysis, anifrolumab-fnia exhibited non-linear PK due to IFNAR1-mediated drug clearance. Following the administration of anifrolumab-fnia at a dose of 300 mg via intravenous infusion every 4 weeks, the estimated systemic clearance (CL) for anifrolumab-fnia was 0.193 L/day.

Specific Populations-                                                                                                     There was no clinically meaningful difference in systemic clearance based on age, race, ethnicity, region, gender, IFN status or body weight, that requires dose adjustment. Age: Based on population PK analyses, age (range 18 to 69 years) did not affect anifrolumab-fnia clearance.

Limited PK data are available for elderly patients; 3% (n=20) of the patients included in the PK analysis were 65 years or older

Renal Impairment:                                                                                                            No specific clinical studies have been conducted to investigate the effect of renal impairment on anifrolumab-fnia.

Hepatic Impairment:                                                                                                         No specific clinical studies have been conducted to investigate the effect of hepatic impairment on anifrolumab-fnia. IgG1 monoclonal antibodies are predominantly eliminated via catabolism and are not expected to undergo hepatic metabolism; changes in hepatic function are not expected to influence anifrolumab-fnia clearance.

Drug Interactions-                                                                                                             No formal drug-drug interaction studies have been conducted.

 USE IN SPECIFIC POPULATIONS

1 Pregnancy Pregnancy-

Exposure Registry -A pregnancy exposure registry monitors pregnancy outcomes in women exposed to SAPHNELO during pregnancy.

 Risk Summary-                                                                                                             The limited human data with SAPHNELO use in pregnant women are insufficient to inform on drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcome.

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

The estimated background risk of major birth defects and miscarriage for 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.

Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk: Pregnant women with SLE are at increased risk of adverse pregnancy outcomes, including worsening of the underlying disease, premature birth, miscarriage, and intrauterine growth restriction.

2. Lactation Risk Summary-                                                                                           No data are available regarding the presence of SAPHNELO in human milk, the effects on the breastfed child, or the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for anifrolumab-fnia and any potential adverse effects on the breast-fed child from anifrolumab-fnia or from the underlying maternal condition.

3. Pediatric Use-                                                                                                            The safety and efficacy of SAPHNELO in pediatric patients less than 18 years of age have not been established.

4. Geriatric Use-                                                                                                                  Of the 664 patients with SLE exposed to anifrolumab-fnia in clinical trials, 3% (n=20) were 65 and over. The number of patients aged 65 years of age and older was not sufficient to determine whether they respond differently from younger adult patients.