INTERACTIONS Formal drug interaction studies have not been performed with BENLYSTA. In clinical trials, BENLYSTA was administered concomitantly with other drugs, including corticosteroids, antimalarials, immunomodulatory and immunosuppressive agents (including azathioprine, cyclophosphamide, methotrexate, and mycophenolate), angiotensin pathway antihypertensives, HMG‑CoA reductase inhibitors (statins), and/or non-steroidal anti-inflammatory drugs (NSAIDs) without evidence of a clinically meaningful effect of these concomitant medications on belimumab pharmacokinetics. The effect of belimumab on the pharmacokinetics of other drugs has not been evaluated [see Clinical Pharmacology ( 12.3 )] .
BENLYSTA is contraindicated in patients who have had anaphylaxis with belimumab. Previous anaphylaxis to belimumab. ( 4 )
AND PRECAUTIONS
- Serious Infections: Serious and sometimes fatal infections have occurred in patients receiving immunosuppressive agents, including BENLYSTA. Use with caution in patients with severe or chronic infections. Consider interrupting therapy with BENLYSTA if patients develop a new infection during treatment with BENLYSTA. ( 5.1 )
- Progressive Multifocal Leukoencephalopathy (PML): Evaluate patients with new-onset or deteriorating neurological signs and symptoms for PML. If PML is suspected, immunosuppressant therapy, including BENLYSTA, must be suspended until PML has been excluded. If PML is confirmed, immunosuppressant therapy, including BENLYSTA, must be discontinued. ( 5.1 )
- Hypersensitivity Reactions, including Anaphylaxis: Serious and fatal reactions have been reported. ( 5.2 )
- Depression and Suicidality: Depression and suicidality were reported in trials with BENLYSTA. Assess for depression and risk of suicide before treatment with BENLYSTA and monitor during treatment. Instruct patients to contact their healthcare provider if new or worsening depression, suicidal thoughts, or other mood changes occur. ( 5.3 )
- Immunization: Live vaccines should not be given concurrently with BENLYSTA. ( 5.5 )
5.1 Serious Infections Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including BENLYSTA. Overall, the incidence of serious infections in controlled trials was similar in subjects receiving BENLYSTA compared with placebo, whereas fatal infections occurred more frequently in subjects receiving BENLYSTA <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> . Consider the risk and benefit before initiating treatment with BENLYSTA in patients with severe or chronic infections. Consider interrupting therapy with BENLYSTA in patients who develop a new infection while receiving it and monitor these patients closely.
Progressive Multifocal
Leukoencephalopathy (PML) Cases of JC virus-associated PML resulting in neurological deficits, including fatal cases, have been reported in patients with SLE receiving immunosuppressants, including BENLYSTA. Risk factors for PML include treatment with immunosuppressant therapies and impairment of immune function. Consider the diagnosis of PML in any patient presenting with new-onset or deteriorating neurological signs and symptoms and consult with a neurologist or other appropriate specialist as clinically indicated. In patients with suspected PML, immunosuppressant therapy, including BENLYSTA, must be suspended until PML has been excluded. If PML is confirmed, immunosuppressant therapy, including BENLYSTA, must be discontinued.
5.2 Hypersensitivity Reactions, including Anaphylaxis Acute hypersensitivity reactions, including anaphylaxis and death, and infusion-related reactions have been reported in association with BENLYSTA <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> . These events generally occurred within hours of the infusion; however, they may occur later. Non-acute hypersensitivity reactions including rash, nausea, fatigue, myalgia, headache, and facial edema have been reported and typically occurred up to a week following the most recent infusion. Hypersensitivity, including serious reactions, has occurred in patients who have previously tolerated infusions of BENLYSTA. Limited data suggest that patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk. Due to overlap in signs and symptoms, it was not possible to distinguish between hypersensitivity reactions and infusion-related reactions in all cases. In the controlled clinical trials of BENLYSTA administered intravenously in adults with SLE, some subjects (13%) received premedication, which may have mitigated or masked a hypersensitivity response or infusion-related reaction; however, there is insufficient evidence to determine whether premedication diminishes the frequency or severity of hypersensitivity reactions or infusion-related reaction. BENLYSTA for intravenous use should be administered by healthcare providers prepared to manage anaphylaxis and infusion-related reactions. Healthcare providers should be aware of the risk of hypersensitivity reactions, which may present as infusion-related reactions. In the event of a serious reaction, discontinue BENLYSTA immediately and administer appropriate medical therapy. With intravenous administration, the infusion rate may be slowed or interrupted if the patient develops an infusion reaction. Monitor patients during infusion and for an appropriate period of time after intravenous administration of BENLYSTA. Consider administering premedication as prophylaxis prior to intravenous dosing <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.1 , 2.2 )]</span> . Inform patients receiving BENLYSTA of the signs and symptoms of hypersensitivity reactions and instruct them to seek immediate medical care should a reaction occur.
5.3 Depression and Suicidality In controlled clinical trials, depression and suicidality were reported in subjects receiving BENLYSTA <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> . Assess the risk of depression and suicide considering the patient’s medical history and current psychiatric status before treatment with BENLYSTA and continue to monitor patients during treatment. Instruct patients receiving BENLYSTA (and caregivers, if applicable) to contact their healthcare provider if they experience new or worsening depression, suicidal thoughts or behavior, or other mood changes. Consider the risk and benefit of continued treatment with BENLYSTA for patients who develop such symptoms.
5.4 Malignancy There is an increased risk of malignancies with the use of immunosuppressants. The impact of treatment with BENLYSTA on the development of malignancies is not known <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> . Consider the individual benefit-risk in patients with known risk factors for the development or reoccurrence of malignancy prior to prescribing BENLYSTA. In patients who develop malignancies, consider the risk and benefit of continued treatment with BENLYSTA.
5.5 Immunization Because of its mechanism of action, BENLYSTA may interfere with the response to immunizations. Live vaccines should not be given for 30 days before or concurrently with BENLYSTA as clinical safety has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving BENLYSTA or the effect of BENLYSTA on new immunizations.
5.6 Concomitant Use with Other Biologic Therapies Available data do not support the safety and efficacy of concomitant use of BENLYSTA with rituximab in patients with SLE. An increased incidence of serious infections and post-injection systemic reactions in subjects receiving BENLYSTA concomitantly with rituximab compared to subjects receiving BENLYSTA alone has been observed <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> . The safety and efficacy of BENLYSTA concomitantly with other biologic therapies, including B-cell-targeted therapies, have not been established. Caution should be exercised if BENLYSTA is administered in combination with other biologic therapies <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5 )]</span> .