Narsoplimab
FDA Drug Information • Also known as: Yartemlea
- Brand Names
- Yartemlea
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Narsoplimab-wuug, a mannan-binding lectin-associated serine protease 2 (MASP-2) inhibitor, is a recombinant human immunoglobulin G4 (IgG4) monoclonal antibody produced in Chinese Hamster Ovary cells. The approximate molecular weight is 143 kDa. YARTEMLEA (narsoplimab-wuug) injection is a sterile, preservative-free, clear to slightly opalescent, slightly yellow to yellow-brown solution for intravenous infusion. Each 2-mL single-dose glass vial contains 370 mg of narsoplimab-wuug, arginine hydrochloride (84.3 mg), citric acid monohydrate (1.42 mg), polysorbate 80 (0.2 mg), sodium citrate (8.6 mg), and Water for Injection, USP. Sodium hydroxide and hydrochloric acid were added to adjust the pH to 5.8.
What Is Narsoplimab Used For?
1 INDICATIONS AND USAGE YARTEMLEA is indicated for the treatment of adult and pediatric patients 2 years of age and older with hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA). YARTEMLEA is a MASP-2 inhibitor indicated for the treatment of adult and pediatric patients 2 years of age and older with hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA). ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Weight (kg) Recommended Dosage Greater than or equal to 50 kg 370 mg given as an intravenous infusion over 30 minutes once weekly. Increase frequency to twice weekly if there is inadequate improvement in TA-TMA signs and symptoms. ( 2.1 ) Less than 50 kg 4 mg/kg given as an intravenous infusion over 30 minutes once weekly. Increase frequency to twice weekly if there is inadequate improvement in TA-TMA signs and symptoms. ( 2.1 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.2 , 2.3 , 2.4 , 2.5 ) 2.1 Recommended Dosage The recommended dosage of YARTEMLEA is provided in Table 1 . Table 1: Recommended Dosage of YARTEMLEA in Adult and Pediatric Patients Two Years of Age and Older with TA-TMA Weight (kg) Recommended Dosage Greater than or equal to 50 kg 370 mg given as an intravenous infusion over 30 minutes once weekly. Increase frequency to twice weekly if there is inadequate improvement in TA-TMA signs and symptoms. Less than 50 kg 4 mg/kg given as an intravenous infusion over 30 minutes once weekly. Increase frequency to twice weekly if there is inadequate improvement in TA-TMA signs and symptoms. If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time. 2.2 Important Preparation and Administration Instructions Administer diluted YARTEMLEA as an intravenous infusion through a polyvinyl chloride (PVC) or PVC-lined infusion line with a 0.2-micron polyethersulfone (PES) in-line filter and a polyurethane catheter. For adults and pediatric patients weighing 10 kg or more , prepare YARTEMLEA in an intravenous bag, diluted to final concentration of 0.8 mg/mL to 8 mg/mL and administer by gravity infusion or via an infusion pump [see Dosage and Administration ( 2.3 and 2.5 )] . For pediatric patients weighing less than 10 kg , prepare YARTEMLEA in a polypropylene syringe, diluted to final concentration of 0.8 mg/mL and administer via a syringe pump [see Dosage and Administration ( 2.4 and 2.5 )] . 2.3 Preparation Instructions into an Intravenous Bag This section describes preparation of YARTEMLEA for adults and pediatric patients weighing 10 kg or more in an intravenous bag. 1. Preparation Use aseptic technique to prepare YARTEMLEA. Parenteral drug-product vial should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. YARTEMLEA is a clear to slightly opalescent, slightly yellow to yellow-brown solution. If discoloration or particles are observed in the vial, discard it. Calculate the dose (mg) based on the patient's body weight and the total volume (mL) of YARTEMLEA solution required. Remove the YARTEMLEA vial from the refrigerator and allow the vial to come to room temperature (18°C to 25°C [64°F to 77°F]) for 30 minutes. Vial must be used to prepare the appropriate dosing solution within 4 hours following removal from refrigerated storage. 2....
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Infections [see Warnings and Precautions ( 5.1 )] Most common adverse reactions (incidence > 20% and independent of causality) are viral infections, sepsis, hemorrhage, diarrhea, vomiting, nausea, neutropenia, pyrexia, fatigue and hypokalemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Omeros Corporation at 1-844-YARTEM1 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial 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 data described in this section reflect exposure to YARTEMLEA in the TA-TMA Study in which 28 adult patients received YARTEMLEA. In total, 24 patients received YARTEMLEA at a dose of 4 mg/kg intravenously once weekly for 4 or 8 weeks and 4 patients received 370 mg intravenously weekly for 8 weeks [see Clinical Studies ( 14 )] . The median duration of treatment with YARTEMLEA was 8 weeks (range: 2 to 16.4 weeks). Serious adverse reactions were reported in 61% of patients receiving YARTEMLEA. Serious adverse reactions in > 5% of patients who received YARTEMLEA included acute kidney injury, confusional state, acute respiratory failure, neutropenic sepsis, septic shock, pulmonary edema, and vomiting. Fatal adverse reactions occurred in 7% of patients, including neutropenic sepsis and septic shock. Adverse reactions leading to dosage interruptions occurred in 7% of patients who received YARTEMLEA and included Escherichia sepsis, pyrexia, pulmonary alveolar hemorrhage, and acute myocardial infarction. The most common adverse reactions (≥ 20%) were viral infections, sepsis, hemorrhage, diarrhea, vomiting, nausea, neutropenia, pyrexia, fatigue, and hypokalemia. Table 2 summarizes the adverse reactions, without regard to causality or relatedness to YARTEMLEA, in the TA-TMA Study. Table 2: Adverse Reactions (≥ 15%) in Patients Receiving YARTEMLEA in the TA-TMA Study * Grouped terms Adverse Reaction All Grades n (%) N = 28 Grade ≥ 3 n (%) N = 28 Hemorrhage* 12 (43) 2 (7) Diarrhea 10 (36) 2 (7) Infection, viral* 10 (36) 2 (7) Neutropenia* 10 (36) 10 (36) Pyrexia 10 (36) 1 (4) Vomiting 9 (32) 2 (7) Fatigue* 8 (29) 1 (4) Hypokalemia* 7 (25) 3 (11) Nausea 7 (25) 1 (4) Sepsis* 7 (25) 6 (21) Pneumonia* 5 (18) 4 (14) Hypotension* 5 (18) 3 (11) Abdominal pain* 5 (18) 1 (4) Anemia* 5 (18) 3 (11) Back pain 5 (18) 0 (0) An additional 221 adult and pediatric patients with TA-TMA were treated with YARTEMLEA in a global expanded access program (EAP) that included patients for whom YARTEMLEA was their initial treatment following diagnosis of TA-TMA as well as patients who had previously failed or stopped other treatments. The median number of YARTEMLEA doses received by the 221 patients in the EAP was 8 and the median duration of therapy was 5.5 weeks. No new clinically significant safety signals were identified in patients treated in the EAP.
Contraindications
4 CONTRAINDICATIONS None None ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary The available data on the use of YARTEMLEA during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, narsoplimab-wuug was administered subcutaneously and intravenously twice weekly to pregnant mice and rabbits during organogenesis at dose exposures up to 22 and 91-fold, respectively, the human exposure at the maximum recommended human dose (MRHD) based on area under the concentration-time curve (AUC). There were no adverse effects observed in the absence of maternal toxicity (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses and peaks during the third trimester. Therefore, it is expected that YARTEMLEA, following administration, will be present in infants exposed in utero during the third trimester. The potential clinical impact of narsoplimab-wuug exposure on infants exposed in utero should be considered. Data Animal Data Narsoplimab-wuug was administered to pregnant mice at doses of 50, 150, or 300 mg/kg by subcutaneous injection and 300 mg/kg by intravenous injection approximately twice weekly during the major period of organogenesis. Intravenous administration caused reduced body weight gain in dams, reduced fetal body weight up to 4.8%, and an increase of approximately 33% in post-implantation loss at 22-fold the exposure expected at the MRHD (based on AUC) of 4 mg/kg intravenously once weekly in humans. Narsoplimab-wuug was...
Overdosage
10 OVERDOSAGE There is no known antidote for YARTEMLEA and YARTEMLEA is not dialyzable. If an overdose occurs, institute general supportive measures. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING YARTEMLEA (narsoplimab-wuug) injection is a sterile, preservative-free, clear to slightly opalescent, slightly yellow to yellow-brown solution supplied as one 370 mg/2 mL (185 mg/mL) single-dose vial in a carton (NDC 62225-300-00). Store YARTEMLEA vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of use. Do not freeze. Do not shake. Do not use beyond the expiration date stamped on the carton.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.