SAPHNELO

SAPHNELO- anifrolumab injection, solution
AstraZeneca Pharmaceuticals LP

1 INDICATIONS AND USAGE

SAPHNELO (anifrolumab-fnia) is indicated for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE), who are receiving standard therapy [see Clinical Studies (14)].

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.

2 DOSAGE AND ADMINISTRATION

2.1 Dosage Recommendations

SAPHNELO must be diluted prior to intravenous administration [see Dosage and Administration (2.2)].

The recommended dosage of SAPHNELO is 300 mg, administered as an intravenous infusion over a 30-minute period, every 4 weeks.

Missed dose

If a planned infusion is missed, administer SAPHNELO as soon as possible. Maintain a minimum interval of 14 days between infusions.

2.2 Instructions for Preparation and Administration

SAPHNELO is supplied as a single-dose vial. Prepare the diluted infusion solution using aseptic technique, by the following procedure:

1.
Visually inspect the vial for particulate matter and discoloration. SAPHNELO is a clear to opalescent, colorless to slightly yellow, solution. Discard the vial if the solution is cloudy, discolored or visible particles are observed. Do not shake the vial.
2.
Withdraw and discard 2 mL of solution from a 50 mL or 100 mL 0.9% Sodium Chloride Injection, USP infusion bag.
3.
Withdraw 2 mL of solution from the vial of SAPHNELO and add it to the infusion bag. Mix the solution by gentle inversion. Do not shake.
4.
Each vial is intended for one time use only. Discard any unused portion remaining in the vial.
5.
Administer the infusion solution immediately after preparation.
6.
If the infusion solution is not administered immediately, store the diluted solution of SAPHNELO at room temperature (59°F to 77°F, 15°C to 25°C) for up to 4 hours, or refrigerated (36°F to 46°F, 2°C to 8°C) for up to 24 hours. Do not freeze. Protect from light. If refrigerated, allow the diluted SAPHNELO solution to reach room temperature prior to administration.
7.
Administer the infusion solution intravenously over a 30-minute period through an infusion line containing a sterile, low-protein binding 0.2 to 15 micron in-line or add-on filter.
8.
To ensure the complete dose of SAPHNELO has been administered, flush the entire infusion line with 25 mL of 0.9% Sodium Chloride Injection, USP at the end of the infusion.
9.
Do not co-administer other medicinal products through the same infusion line.
10.
Dispose of any unused medicinal product or waste material in accordance with local requirements .

3 DOSAGE FORMS AND STRENGTHS

Injection: 300 mg/2 mL (150 mg/mL) as a clear to opalescent, colorless to slightly yellow, solution in a single-dose vial.

4 CONTRAINDICATIONS

SAPHNELO is contraindicated in patients with a history of anaphylaxis with anifrolumab-fnia [see Warnings and Precautions (5.2)].

5 WARNINGS AND PRECAUTIONS

5.1 Serious Infections

Serious and sometimes fatal infections (including COVID‑19) have occurred in patients receiving immunosuppressive agents, including SAPHNELO. Overall, the incidence of serious infections in controlled trials was similar in patients receiving SAPHNELO compared with placebo, whereas fatal infections occurred more frequently in patients receiving SAPHNELO [see Adverse Reactions (6.1)].

In controlled trials, SAPHNELO increased the risk of respiratory infections and herpes zoster (disseminated herpes zoster events have been reported) [see Adverse Reactions (6.1) ].

Consider the benefit and risk of administering SAPHNELO in patients with a chronic infection, a history of recurrent infections, or known risk factors for infection. Avoid initiating treatment with SAPHNELO in patients with any clinically significant active infection until the infection resolves or is adequately treated. Instruct patients to seek medical advice if signs or symptoms of clinically significant infection occur. If a patient develops an infection, or is not responding to standard anti-infective therapy, monitor the patient closely and consider interrupting SAPHNELO therapy until the infection resolves.

5.2 Hypersensitivity Reactions Including Anaphylaxis

Serious hypersensitivity reactions (including anaphylaxis) have been reported following SAPHNELO administration [see Contraindication (4)]. Events of angioedema have also been reported [see Adverse Reactions (6.1)].

Other hypersensitivity reactions and infusion-related reactions have occurred following administration of SAPHNELO [see Adverse Reactions (6.1)]. Consider pre-medication before infusion of SAPHNELO for patients with a history of these reactions.

SAPHNELO should be administered by healthcare providers prepared to manage hypersensitivity reactions, including anaphylaxis, and infusion-related reactions. If a serious infusion-related or hypersensitivity reaction (e.g., anaphylaxis) occurs, immediately interrupt the administration of SAPHNELO and initiate appropriate therapy.

5.3 Malignancy

There is an increased risk of malignancies with the use of immunosuppressants. The impact of SAPHNELO treatment on the potential development of malignancies is not known.

Consider the individual benefit-risk in patients with known risk factors for the development or reoccurrence of malignancy prior to prescribing SAPHNELO. In patients who develop malignancies, consider the benefit-risk of continued treatment with SAPHNELO.

5.4 Immunizations

Update immunizations, according to current immunization guidelines, prior to initiating SAPHNELO therapy. Avoid concurrent use of live or live-attenuated vaccines in patients treated with SAPHNELO.

5.5 Not Recommended for Concomitant Use with Other Biologic Therapies

SAPHNELO has not been studied in combination with other biologic therapies, including B-cell-targeted therapies. Therefore, use of SAPHNELO is not recommended for use in combination with biologic therapies.

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are also discussed elsewhere in the labeling:

Serious Infections [see Warnings and Precautions (5.1)]
Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions (5.2)]
Malignancy [see Warnings and Precautions (5.3)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of SAPHNELO was assessed through 52 weeks in patients with moderate to severe SLE who received anifrolumab-fnia 300 mg by intravenous infusion every 4 weeks (N=459), compared to placebo (N=466) in controlled clinical trials (Trials 1, 2 and 3) [see Clinical Studies (14)]. The population studied had a mean age of 41 years (range: 18 to 69), of which 93% were female, 60% White, 13% Black/African American, and 10% Asian.

In the controlled-clinical trials, adverse reactions, irrespective of causality, were reported in 87% of patients receiving SAPHNELO and 79% of patients receiving placebo.

Adverse reactions that occurred at greater than or equal to 2% incidence are shown in Table 1.

Table 1 Adverse Reactions Occurring in ≥2% of Patients on SAPHNELO 300 mg (Trials 1, 2 and 3) at 52 weeks
*
Upper respiratory tract infections (including Upper respiratory tract infections, Nasopharyngitis, Pharyngitis)
Bronchitis (including Bronchitis, Bronchitis viral, Tracheobronchitis)
Respiratory tract infection (including Respiratory tract infection, Respiratory tract infection viral, Respiratory tract infection bacterial)

Adverse Reaction

SAPHNELO

(N=459)

%

Placebo

(N=466)

%

Upper respiratory tract infection *

34

23

Bronchitis

11

5.2

Infusion‑related reactions

9.4

7.1

Herpes Zoster

6.1

1.3

Cough

5.0

3.2

Respiratory tract infection

3.3

1.5

Hypersensitivity

2.8

0.6

All patients received standard therapy.

Long-term Safety

Patients who completed Trials 2 and 3 (Phase III feeder trials) were eligible to continue on treatment in a randomized, double-blind, placebo-controlled long-term extension (LTE) study, for an additional 3 years. The long-term safety of SAPHNELO was assessed in 257 patients who received anifrolumab-fnia 300 mg and 112 patients who received placebo in both a feeder trial and the LTE. Of these, 177 patients who received SAPHNELO (68.9%) and 52 patients who received placebo (46.4%) completed a total of 4 years on treatment. The overall long-term safety profile of SAPHNELO was consistent with Trials 1, 2 and 3.

Specific Adverse Reactions

Infections

In the 52‑week controlled-clinical trials, infections were reported in a greater proportion of patients while on treatment with SAPHNELO compared to placebo (69.7% [320/459] versus 55.4% [258/466]), corresponding to exposure-adjusted incidence rates (EAIR) of 141.8 and 99.9 per 100 patient years (PY), respectively.

Serious Infections

In the 52‑week controlled-clinical trials, the incidence of serious infections while on treatment was 4.8% (22/459) in patients treated with SAPHNELO compared with 5.6% (26/466) in patients receiving placebo, corresponding to EAIR of 5.4 and 6.6 per 100 PY, respectively. The most frequent serious infection was pneumonia.

In the 52‑week controlled-clinical trials, fatal infections occurred in 0.4% of patients receiving SAPHNELO and 0.2% of the patients receiving placebo.

During the LTE study, the most common serious infections were COVID-19 and pneumonia.

Herpes Zoster

In the 52‑week controlled-clinical trials, the incidence of herpes zoster in patients while on treatment with SAPHNELO was 6.1% (28/459) and 1.3% (6/466) in patients on placebo, corresponding to EAIRs of 6.9 and 1.5 per 100 PY, respectively. Cases with multidermatomal involvement and disseminated presentation have been reported. Of the 28 SAPHNELO-treated patients with herpes zoster, 2 experienced disseminated disease requiring hospitalization compared to none among patients who received placebo.

Hypersensitivity Reactions Including Anaphylaxis

During the SLE development program, there was one report of an anaphylactic reaction in a patient who received 150 mg anifrolumab-fnia, and 4 reports of angioedema after 300 mg. In general, the hypersensitivity reactions were predominantly mild or moderate in intensity and did not lead to discontinuation of SAPHNELO.

In the 52‑week controlled-clinical trials, hypersensitivity reactions occurred in 2.8% (13/459) of patients while on treatment with SAPHNELO and 0.6% (3/466) of patients on placebo, corresponding to EAIR of 3.2 and 0.7 per 100 PY, respectively. Serious hypersensitivity reactions were reported for 0.6% (3/459) of patients receiving SAPHNELO, including angioedema (n=2).

Infusion-related Reactions

Infusion-related reactions were mild to moderate in intensity; the most common symptoms were headache, nausea, vomiting, fatigue, and dizziness.

In the 52‑week controlled-clinical trials, the incidence of infusion-related reactions while on treatment was 9.4% (43/459) in patients while on treatment with SAPHNELO and 7.1% (33/466) in patients on placebo, corresponding to EAIRs of 11.1 and 8.7 per 100 PY, respectively.

Malignancies

In 52‑week controlled-clinical trials, malignancies (excluding non-melanoma skin cancers) were observed in 0.7% (3/459) and 0.6% (3/466) of patients receiving SAPHNELO and placebo, corresponding to EAIR of 0.7 and 0.7 per 100 PY, respectively. Malignant neoplasm (including non-melanoma skin cancers) was reported for 1.3% (6/459) patients receiving SAPHNELO, compared to 0.6% (3/466) patients receiving placebo (EAIR: 1.3 and 0.7 per 100 PY, respectively). The malignancies that were reported in more than one patient treated with SAPHNELO included breast cancer and squamous cell carcinoma.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.