generally occurred within hours of infusion; however, they may occur later; non-acute hypersensitivity reactions including rash, nausea, fatigue, myalgia, headache, and facial edema 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 the drug; limited data suggest that patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk Therapy should be administered by healthcare providers prepared to manage anaphylaxis; in the event of a serious reaction, discontinue treatment immediately and administer appropriate medical therapy; monitor patients during infusion and for an appropriate period of time after intravenous administration of the drug Consider administering premedication as prophylaxis prior to intravenous dosing; Inform patients receiving the drug of the signs and symptoms of hypersensitivity reactions and instruct them to seek immediate medical care should a reaction occur Infusion reactions Serious infusion reactions (excluding hypersensitivity reactions) reported, including bradycardia, myalgia, headache, rash, urticaria, and hypotension; most common reactions included headache, nausea, and skin reactions; consider administering premedication as prophylaxis prior to intravenous dosing For intravenous use, therapy should be administered by healthcare providers prepared to manage infusion reactions; infusion rate may be slowed or interrupted if patient develops a reaction; monitor during and for an appropriate period of time after infusion Healthcare providers should be aware of risk of hypersensitivity reactions, which may present as infusion reactions, and monitor patients closely; instruct patients to seek immediate medical care should a reaction occur Depression and suicidality In clinical trials, psychiatric events were associated with IV administration in SLE patients Before treatment, assess risk of depression and suicide considering the patient’s medical history and current psychiatric status Continue to monitor during treatment Instruct patients to contact healthcare provider if new or worsening depression arises, suicidal thoughts or behavior, or other mood changes; assess risk and benefit of continued therapy for patients who develop such symptoms Consider risk and benefit of continued treatment for patients who develop symptoms of depression or suicidality Drug interaction overview Immunizations Do not administer live vaccines 30 days before or concurrently with belimumab May decrease response to immunizations Other biologic therapies Coadministration not recommended Not studied in combination with other biologic therapies (eg, B-cell targeted therapies) Concomitant use with rituximab increased incidence of serious infections and post-injection systemic reactions observed Pregnancy There is a pregnancy exposure registry that evaluates pregnancy outcomes in women with lupus exposed to this therapy during pregnancy; healthcare professionals are encouraged to refer patients and pregnant women are encouraged to enroll themselves by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing-study/benlysta-belimumab/ Data 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, including worsening of the underlying disease, premature birth, spontaneous abortion, and intrauterine growth restriction Clinical considerations Maternal lupus nephritis increases the risk of hypertension and preeclampsia/eclampsia Passage of maternal antiphospholipid antibodies across the placenta may result in adverse neonatal outcomes, including neonatal lupus and congenital heart block Monoclonal antibodies, such as belimumab, are actively transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero-exposed infant Use during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus Contraception Following an assessment of benefit versus risk, if prevention of pregnancy is warranted, females of reproductive potential should use effective contraception during treatment and for at least 4 months after the final treatment Lactation Passage of maternal antiphospholipid antibodies across the placenta may result in adverse neonatal outcomes, including neonatal lupus and congenital heart block Monoclonal antibodies, such as belimumab, are actively transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero-exposed infant Use during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus Because maternal antibodies are excreted in human breast milk, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of breastfeeding to the infant and the importance of the drug to the motherPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Inhibits the biological activity of B-lymphocyte stimulator (BLyS); BLyS is a naturally occurring protein required for survival and development of B-lymphocyte cells into mature plasma B cells that produce antibodies In autoimmune diseases, elevated BLyS levels are thought to contribute to production of autoantibodies Belimumab specifically recognizes and binds to BLyS, inhibits BLyS’s stimulation of B-cell development, and finally, restores the potential for autoantibody-producing B cells to undergo the normal process of apoptosis (programmed cell death) Absorption Peak plasma concentration: 313 mcg/mL (IV); 108 mcg/mL (SC) AUC: 3,083 days•mcg/mL (IV); 726 days•mcg/mL (SC) Distribution Vd (steady-state): 5 L Half-life, distribution: 1.8 days (IV); 1.1 days (SC) Elimination Half-life, terminal: 19.4 days (IV); 18.3 days (SC) Clearance: 215 mL/day (IV); 204 mL/day (SC) IV Compatibilities 0.9% NaCl 0.45% NaCl Lactated Ringer solution IV Incompatibilities Dextrose solutions IV Preparation Lyophilized powder in a single-use vial for intravenous infusion only and should be reconstituted and diluted using aseptic technique Remove vial from refrigerator; let stand for 10-15 minutes to reach room temperature Reconstitution Remove vial from refrigerator; allow vial to reach room temperature for 10-15 min Reconstitute with 1.5 mL (120-mg vial) and 4.8 mL (400-mg vial) of sterile water for injection to final concentration of 80 mg/mL Direct stream of sterile water toward side of vial to minimize foaming DO NOT SHAKE; gently swirl vial for 60 seconds every 5 minutes until powder is dissolved Reconstitution is typically complete within 10-15 minutes, but may take up to 30 minutes Note: If mechanical reconstitution device is used, it should not exceed 500 rpm and vial swirled for no longer than 30 minutes Once reconstituted, solution should be opalescent and colorless to pale yellow, and without particles; small air bubbles are expected and acceptable Dilution Dilute reconstituted solution in 250-mL infusion bag (ie, 0.9% NaCl, 0.45% NaCl, LR) OR in 100-mL infusion bag if patient weighs <40 kg Withdraw and discard volume equal to volume of the reconstituted solution required for dose Add required volume of reconstituted solution to infusion bag/bottle (final concentration should not exceed 4 mg/mL) Gently invert bag/bottle to mix the solution Visually inspect for particulate matter and discoloration before administration, whenever solution and container permits Discard any unused portion Total time from reconstitution to completion of infusion should not exceed 8 hours IV Administration Administer diluted solution IV over 1 hour Administer by health care providers prepared to manage anaphylaxis Do not infuse concomitantly in same IV line with other drugs Consider administering premedication (ie, antihistamines, corticosteroids) for prophylaxis against infusion reactions and hypersensitivity SC Preparation Instruct patient to remove the autoinjector or prefilled syringe from the refrigerator and allow it to sit at room temperature for 30 minutes prior to the SC injection; do not warm drug in any other way Visually inspect the window of the autoinjector or the prefilled syringe for particulate matter or discoloration; solution should be clear to opalescent and colorless to pale yellow Do not use if the product exhibits discoloration or particulate matter Instruct the patient not to use autoinjector or prefilled syringe if dropped on a hard surface SC Administration SC route only for adults aged ≥18 years Administer SC once weekly, preferably on the same day each week Administer SC in abdomen or thigh When injecting in the same body region, advise to use a different injection site for each injection; never give injections into areas where the skin is tender, bruised, red, or hard When a 400-mg dose is administered at same site, it is recommended that the 2 individual 200-mg injections be administered at least 5 cm (~2 inches) apart Missed dose Administer missed dose as soon as the patient remembers Thereafter, the patient can resume dosing on their usual day of administration or start a new weekly schedule from the day that the missed dose was administered Not recommended to administer 2 doses on the same day Storage Unopened IV vials Store refrigerated 2-8ºC (36-46ºF); do not freeze Store vials in original carton and protect from light until use Avoid exposure to heat Reconstituted IV vials If not used immediately, may be stored refrigerated 2-8ºC (36-46ºF) For single use only; discard any unused portion Diluted IV solution Refrigerate at 2-8ºC (36-46ºF) or at room temperature Total time from reconstitution to completion of infusion should not exceed 8 hours SC prefilled syringes or autoinjector Refrigerated Refrigerate prefilled syringe or autoinjectors at 2-8°C (36-46°F) Keep product in the original carton to protect from light until the time of use Do not freeze, shake, or expose to heat Nonrefrigerated May be stored outside of the refrigerator up to 86°F (30°C) for up to 12 hr in the original container Do not use and do not place back in refrigerator if left out for >12 hr BRAND FORM. UNIT PRICE PILL IMAGE Benlysta intravenous- 120 mg vialBenlysta intravenous- 400 mg vialBenlysta subcutaneous- 200 mg/mL solutionBenlysta subcutaneous- 200 mg/mL syringeBenlysta subcutaneous- 200 mg/mL syringeCopyright © 2010 First DataBank, Inc.Print Patient Educationbelimumab intravenous BELIMUMAB - INJECTION (be-LIM-ue-mab) COMMON BRAND NAME(S): Benlysta USES: This medication is used with other medications to treat certain types of lupus. Belimumab belongs to a class of drugs known as monoclonal antibodies. It works by decreasing the effect of a certain protein that is increased in people with active lupus. This may help decrease some of the symptoms of lupus. HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using belimumab and each time you get a treatment. If you have any questions, ask your doctor or pharmacist.This medication is given by injection into a vein by a health care professional. It should be injected slowly over 1 hour. The first 3 doses are given every 2 weeks. After the third dose, it is usually given every 4 weeks, or as directed by your doctor. The dosage is based on your weight.Your doctor may prescribe other medications for you to take before the start of your treatment to help prevent serious side effects.This medication may cause very serious reactions during or after treatment. These reactions occur more often during the first and second treatments. Your doctor will monitor you closely. If you have a reaction, your treatment will be temporarily stopped. Tell your doctor or nurse right away if any of these effects occur: headache, slow heartbeat, muscle pain, dizziness/fainting, nausea, or rash/itching.Use this medication regularly to get the most benefit from it. It may help to mark your calendar with a reminder.Tell your doctor if your condition does not improve or if it worsens. SIDE EFFECTS: See also How to Use section.Nausea, diarrhea, or trouble sleeping may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: mental/mood changes (such as new/worsening depression, thoughts of suicide).This medication may lower your ability to fight infections. This may make you more likely to get a serious (rarely fatal) infection or make any infection you have worse. Tell your doctor right away if you have any signs of infection (such as sore throat that doesn't go away, fever, chills, cough).Very rarely, people using this medication have developed cancers (including skin cancer). Tell your doctor right away if you develop