Drug information of Belimumab

Mechanism of effect

Belimumab is an IgG1-lambda monoclonal antibody that prevents the survival of B lymphocytes by blocking the binding of soluble human B lymphocyte stimulator protein (BLyS) to receptors on B lymphocytes. This reduces the activity of B-cell mediated immunity and the autoimmune response.

Pharmacodynamic

Belimumab is an IgG1-lambda monoclonal antibody that prevents the survival of B lymphocytes by blocking the binding of soluble human B lymphocyte stimulator protein (BLyS) to receptors on B lymphocytes. This reduces the activity of B-cell mediated immunity and the autoimmune response.

Dosage

Dosing: Adult

Systemic lupus erythematosus (SLE):

IV: Initial: 10 mg/kg every 2 weeks for 3 doses; Maintenance: 10 mg/kg every 4 weeks

SubQ: 200 mg once weekly

Switching from IV therapy: Administer the first SubQ dose 1 to 4 weeks after the last IV dose.

Missed dose: If a dose is missed, administer the dose as soon as possible and then resume the original schedule on the usual day of administration or start a new weekly schedule based on the date that the missed dose was administered.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Consider premedication for prevention of hypersensitivity and infusion reactions.

Systemic lupus erythematosus (SLE):

IV: Children ≥5 years and Adolescents: Initial: 10 mg/kg/dose every 2 weeks for 3 doses; followed by maintenance therapy of 10 mg/kg/dose every 4 weeks.

SubQ: Adolescents ≥18 years: 200 mg once weekly; preferably on the same day each week.

Conversion from IV therapy: Administer the first SubQ dose 1 to 4 weeks after the last IV dose.

Drug contraindications

Hypersensitivity (anaphylaxis) to belimumab or any component of the formulation

Interactions

Alerts

Hypersensitivity/infusion reactions: Acute hypersensitivity reactions including anaphylaxis (with fatalities) have been reported, including patients who had previously tolerated infusions of belimumab; onset may occur within hours of the infusion or may be delayed. Non-acute hypersensitivity reactions, including facial edema, fatigue, headache, myalgia, nausea, and rash have been reported and may occur up to a week following infusion. Risk for hypersensitivity reactions may be increased with history of multiple drug allergies or significant hypersensitivity. Infusion-related reactions (which may be difficult to distinguish from hypersensitivity) may also occur; symptoms may include angioedema, bradycardia, dyspnea, headache, hypotension, myalgia, pruritus, rash, and urticaria. Monitor for hypersensitivity and infusion-related reactions for an appropriate time following administration and immediately discontinue for severe reactions (and administer appropriate medical treatment) or slow or temporarily interrupt infusion for other infusion reactions. It is unknown if premedication prevents or reduces the severity of hypersensitivity reactions.

• Infections: Serious and potentially fatal infections may occur during treatment. Use with caution in patients with severe or chronic infections; treatment should not be undertaken if receiving therapy for chronic infection. Consider interrupting belimumab in patients who develop new infections and initiate appropriate anti-infective treatment; monitor closely.

• Malignancy: Immunosuppressant therapy may increase the risk of malignancy.

• Mortality: Deaths due to infection, cardiovascular disease, and suicide were higher in belimumab patients compared to placebo during clinical trials in adults.

• Progressive multifocal leukoencephalopathy: Cases of progressive multifocal leukoencephalopathy (PML) associated with JC virus (some fatal) have been reported in patients with systemic lupus erythematosus (SLE) receiving immunosuppressants, including belimumab. Risk factors for PML include immunosuppressant therapies and impaired immune function. Consider diagnosis of PML in any patient presenting with new-onset or deteriorating neurologic signs/symptoms; consult a neurologist (or other appropriate specialist). If PML is confirmed, consider discontinuing immunosuppressant treatment, including belimumab.

• Psychiatric events: Psychiatric disorders (including depression and suicidal ideation and behavior) have been reported. Prior to and during treatment, the risk of depression and suicide should be assessed based on medical history and current psychiatric status. Advise patients and caregivers to seek medical attention for manifestations of suicidal ideation or behavior, new-onset or worsening depression, anxiety, or other mood changes; risk and benefit of continued treatment should be assessed for patients who develop such symptoms.

Points of recommendation

IV: To reconstitute, remove vial from the refrigerator and allow to stand 10 to 15 minutes to reach room temperature. Reconstitute 120 mg vial with 1.5 mL of SWFI. Reconstitute 400 mg vial with 4.8 mL of SWFI. A 21- to 25-gauge needle is recommended to use for piercing the vial stopper for reconstitution and dilution. To minimize foaming, direct SWFI toward the side of the vial. Gently swirl for 60 seconds every 5 minutes until powder has dissolved (usual reconstitution time is 10 to 15 minutes, but may take up to 30 minutes); do not shake. If utilizing a mechanical reconstitution device, do not exceed 500 rpm or 30 minutes. Further dilute reconstituted solution in 250 mL (or 100 mL for patients ≤40 kg) of NS, 0.45% NS, or lactated Ringer's by first removing and discarding the volume equivalent to the volume of the reconstituted solution to be added to prepare the appropriate dose; add the appropriate volume of the reconstituted solution to the infusion container and gently invert to mix solution.

SubQ: Remove the autoinjector or prefilled syringe from the refrigerator and allow to sit at room temperature for 30 minutes prior to administration; do not warm product in any other way. Visually inspect the window of the autoinjector or prefilled syringe for particulate matter or discoloration. Do not use if product exhibits discoloration or if dropped on a hard surface.
Administration

IV: Administer IV over 1 hour through a dedicated IV line. Do NOT administer as an IV push or bolus. Discontinue infusion for severe hypersensitivity reaction (eg, anaphylaxis, angioedema). The infusion may be slowed or temporarily interrupted for minor reactions. Consider premedicating with an antihistamine and antipyretic for prophylaxis against hypersensitivity or infusion reactions.

SubQ: Allow prefilled syringe and autoinjector to warm to room temperature for 30 minutes prior to administration; do not warm product in any other way. Administer SubQ using a different injection site on the same day each week; do not administer into tender, bruised, red, or hard skin. Initial use is recommended under supervision of physician; self-injection may occur after proper training.
Storage

IV: Prior to reconstitution, store unused vials between 2°C and 8°C (36°F and 46°F); do not freeze. Protect from light. Avoid exposure to heat. Prior to further dilution in NS, 0.45% NS, or lactated Ringer's, the reconstituted solution must be stored under refrigeration. The diluted solution may be stored refrigerated or at room temperature. Infusion must be completed within 8 hours of reconstitution.

SubQ: Refrigerate prefilled autoinjectors and prefilled syringes at 2°C to 8°C (36°F to 46°F). Keep in original carton to protect from light. Do not freeze. Do not shake. Avoid exposure to heat. May be stored outside of the refrigerator up to 30°C (86°F) for up to 12 hours in the original container. Do not use and do not place back in refrigerator if left out for more than 12 hours.

Pregnancy level

This drug should be used during pregnancy only if the benefit outweighs the risk.

AU TGA pregnancy category: C
US FDA pregnancy category: Not assigned.

Risk Summary: Available data on use of this drug in pregnant women are insufficient to determine whether there is a drug-associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with SLE. Monoclonal antibodies, such as this drug, are actively transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero-exposed infant.

Breast feeding warning