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Introduction

Immunosuppressive agent; type I interferon (IFN) receptor antagonist.

Uses for Anifrolumab (Systemic)

Systemic Lupus Erythematosus

Treatment of moderate to severe systemic lupus erythematosus (SLE) in adults; use in conjunction with other standard SLE therapies (e.g., corticosteroids, antimalarials, immunosuppressant agents).

Not evaluated and therefore not recommended in patients with severe active lupus nephritis or severe active CNS lupus.

The European Alliance of Associations for Rheumatology (EULAR) has provided guidelines on the management of SLE. In the 2019 EULAR guidelines, biologic agents are recommended in patients with an inadequate response to standard therapies; however, anifrolumab was not yet available when these guidelines were published.

Anifrolumab (Systemic) Dosage and Administration

General

Pretreatment Screening

• Consider the potential risks and benefits before initiating anifrolumab in patients with a chronic infection, a history of recurrent infections, or known risk factors for infection.

• Consider the potential risks and benefits before initiating anifrolumab in patients with known risks factors for the development or recurrence of malignancy.

• Update immunizations according to current immunization guidelines prior to initiating treatment with anifrolumab.

Patient Monitoring

• Monitor for signs and symptoms of hypersensitivity and infusion-related reactions.

• Monitor for signs and symptoms of infection during treatment.

Premedication and Prophylaxis

• Consider premedication before infusions in patients with a history of hypersensitivity or infusion-related reactions.

Dispensing and Administration Precautions

• Administer by healthcare providers prepared to manage hypersensitivity reactions and infusion-related reactions.

Administration

IV Administration

Administer by IV infusion over 30 minutes every 4 weeks.

Commercially available as an injection concentrate that must be diluted prior to IV administration.

Anifrolumab injection is preservative-free. Discard any unused portion left in the single-use vial after preparation.

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

Do not administer other medications concomitantly via the same infusion line.

Interrupt the infusion if the patient develops any signs of adverse reactions, including infusion or hypersensitivity reactions.

Dilution

To prepare the diluted infusion solution, withdraw and discard 2 mL of solution from a 50 mL or 100 mL 0.9% sodium chloride injection bag using aseptic technique. Then, withdraw 2 mL (300 mg) of anifrolumab concentrate for injection from the single-use vial, and transfer to the 0.9% sodium chloride injection bag. Gently invert the bag of anifrolumab to mix; do not shake. Use the diluted solution immediately after preparation or store at room temperature for up to 4 hours or under refrigeration for up to 24 hours. If refrigerated, allow the diluted solution to come to room temperature prior to administration.

Rate of Administration

Administer the diluted solution via IV infusion over 30 minutes through an IV line containing a sterile, low-protein binding, in-line or add-on, 0.2–15-micron filter.

Dosage

Adults

Systemic Lupus Erythematosus

IV

300 mg by IV infusion every 4 weeks.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Use

No specific dosage recommendations at this time.

Contraindications

History of anaphylaxis to anifrolumab.

Warnings/Precautions

Serious Infections

Serious, sometimes fatal, infections reported. Increased risk of respiratory infections and herpes zoster (including disseminated herpes zoster).

Consider risks and benefits of anifrolumab in patients with chronic infections, a history of recurrent infections, or known risk factors for infection. Avoid starting anifrolumab during an active infection until infection is treated or resolved. If an infection develops while on anifrolumab therapy or patient is not responsive to standard anti-infective treatment, seek medical treatment for the infection and monitor closely; consider interruption of therapy and closely monitor patient until resolution of the infection.

Hypersensitivity Reactions

Serious hypersensitivity reactions reported following anifrolumab administration; angioedema has also occurred.

Other hypersensitivity and infusion-related reactions have been reported. Consider premedication in patients with a history of these reactions prior to infusion of anifrolumab.

Administer anifrolumab only under the supervision of a healthcare provider prepared to manage hypersensitivity reactions, including anaphylaxis, and infusion-related reactions. If there is a serious infusion-related or hypersensitivity reaction (e.g., anaphylaxis), immediately stop administration and initiate appropriate therapy.

Malignancy

Immunosuppressants are associated with an increased risk of malignancies; specific risk for malignancy development in patients treated with anifrolumab not known.

Prior to initiating anifrolumab, consider benefits and risks in patients with known risk factors for the development or recurrence of malignancy. If malignancy develops during treatment, consider risk versus benefit of continuing anifrolumab.

Immunization

Update immunizations prior to initiation of anifrolumab in accordance with current immunization guidelines. Avoid use of live or live-attenuated vaccines during treatment.

Not Recommended for Concomitant Use with other Biologic Therapies

Not studied and not recommended for use in combination with other biologic agents, including B-cell targeted therapies.

Immunogenicity

Potential for immunogenicity. Anti-anifrolumab antibodies detected. Clinical relevance not known.

Specific Populations

Pregnancy

Limited human data available to inform drug-associated risk. For more information, contact the pregnancy exposure registry that monitors pregnancy outcomes in women exposed to anifrolumab at 1-877-693-9268.

Lactation

Not known whether anifrolumab is distributed into human milk; however, the drug has been detected in animal milk. Consider the benefits of breast-feeding, the potential for adverse effects from anifrolumab exposure to the breast-fed infant, and the mother’s clinical need for anifrolumab.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently from younger adult patients.

Hepatic Impairment

Based on pharmacokinetic analyses, baseline hepatic biomarkers (ALT and AST levels ≤2 times the ULN and total bilirubin) had no clinically relevant effects on anifrolumab clearance.

Renal Impairment

Based on pharmacokinetic analyses, clearance of anifrolumab similar between normal (eGFR >90 mL/minute/1.73 m²) and mild to moderate renal impairment (eGFR 30–89 mL/minute/1.73 m²).

Not evaluated in severe renal impairment or ESRD (eGFR <30 mL/minute/1.73 m²), but anifrolumab is not renally cleared.

Common Adverse Effects

Adverse drug reactions (incidence ≥5%): nasopharyngitis, upper respiratory tract infections, bronchitis, infusion-related reactions, herpes zoster, cough.

General

Pretreatment Screening

• Consider the potential risks and benefits before initiating anifrolumab in patients with a chronic infection, a history of recurrent infections, or known risk factors for infection.

• Consider the potential risks and benefits before initiating anifrolumab in patients with known risks factors for the development or recurrence of malignancy.

• Update immunizations according to current immunization guidelines prior to initiating treatment with anifrolumab.

Patient Monitoring

• Monitor for signs and symptoms of hypersensitivity and infusion-related reactions.

• Monitor for signs and symptoms of infection during treatment.

Premedication and Prophylaxis

• Consider premedication before infusions in patients with a history of hypersensitivity or infusion-related reactions.

Dispensing and Administration Precautions

• Administer by healthcare providers prepared to manage hypersensitivity reactions and infusion-related reactions.

Administration

IV Administration

Administer by IV infusion over 30 minutes every 4 weeks.

Commercially available as an injection concentrate that must be diluted prior to IV administration.

Anifrolumab injection is preservative-free. Discard any unused portion left in the single-use vial after preparation.

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

Do not administer other medications concomitantly via the same infusion line.

Interrupt the infusion if the patient develops any signs of adverse reactions, including infusion or hypersensitivity reactions.

Dilution

To prepare the diluted infusion solution, withdraw and discard 2 mL of solution from a 50 mL or 100 mL 0.9% sodium chloride injection bag using aseptic technique. Then, withdraw 2 mL (300 mg) of anifrolumab concentrate for injection from the single-use vial, and transfer to the 0.9% sodium chloride injection bag. Gently invert the bag of anifrolumab to mix; do not shake. Use the diluted solution immediately after preparation or store at room temperature for up to 4 hours or under refrigeration for up to 24 hours. If refrigerated, allow the diluted solution to come to room temperature prior to administration.

Rate of Administration

Administer the diluted solution via IV infusion over 30 minutes through an IV line containing a sterile, low-protein binding, in-line or add-on, 0.2–15-micron filter.

Dosage

Adults

Systemic Lupus Erythematosus

IV

300 mg by IV infusion every 4 weeks.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Use

No specific dosage recommendations at this time.

No formal drug interaction studies have been conducted.

Specific Drugs