GAMIFANT emapalumab-lzsg 500 mg/20mL Injection
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Interferon gamma Blocker class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Emapalumab-lzsg injection is used to treat primary hemophagocytic lymphohistiocytosis (HLH; a condition in which the immune system overreacts and damages blood cells, the liver, spleen, and other organs) and HLH/macrophage activation syndrome (MAS; a serious or life-threatening condition in which the body attacks its own tissues) in certain patients with Still's disease (a condition that causes inflammation, fever, rash, headache, fatigue, and joint and muscle pain), including systemic juvenile idiopathic arthritis (SJIA). Emapalumab-lzsg injection is in a class of medications called monoclon...
Read the full MedlinePlus article ↗- Gamifant is used to treat a rare but life-threatening condition called hemophagocytic lymphohistiocytosis — HLH for short — where the immune system goes into dangerous overdrive an...
- What exactly is Gamifant being used for?
- No, Gamifant is not a pill. It's given as an IV infusion — a slow drip directly into a vein — and it takes about one hour each time. It's always given in a clinical setting by a he...
- How is this medicine given — do I take a pill?
Patient education
Supplement & herbal interactions
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 4QD397987E
An amino acid used as a buffer and stabilizer in medications. It helps maintain the pH balance and protects the active drug from breaking down during storage and use.
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UNII X573657P6P
Histidine monohydrochloride monohydrate is an amino acid salt used as a buffer in medicines. It helps maintain the proper acidity level of liquid formulations to keep the drug stable and effective.
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UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
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UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
5 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Gamifant 500 mg/20mLthis 66658-0525-01 | Swedish | 1 vial | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Nov 20, 2030 |
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📊 Medicare Part D spend CMS · PART D · 2025 (Q1-Q4)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 66658-0525-01 You're viewing this | 1 VIAL, SINGLE-USE in 1 CARTON (66658-525-01) / 20 mL in 1 VIAL, SINGLE-USE | 2023-06-07 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE GAMIFANT is indicated for the treatment of: adult and pediatric patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy. adult and pediatric patients with HLH/macrophage activation syndrome (MAS) in known or suspected Still’s disease, including systemic Juvenile Idiopathic Arthritis (sJIA), with an inadequate response or intolerance to glucocorticoids, or with recurrent MAS. GAMIFANT is an interferon gamma (IFNγ) neutralizing antibody indicated for the treatment of: adult and pediatric patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy.
( 1 ) adult and pediatric patients with HLH/macrophage activation syndrome (MAS) in known or suspected Still’s disease, including systemic Juvenile Idiopathic Arthritis (sJIA), with an inadequate response or intolerance to glucocorticoids, or with recurrent MAS. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION For intravenous infusion only: Primary HLH recommended starting dosage: 1 mg/kg as an intravenous infusion over 1 hour twice per week. ( 2.1 ) HLH/MAS in Still’s disease recommended dosage schedule: 6 mg/kg, followed by 3 mg/kg every 3 days for 5 doses, then 3 mg/kg twice per week. Given as an intravenous infusion over 1 hour. ( 2.2 ) For both indications, the dose may be titrated up to a maximum of 10 mg/kg. ( 2.5 , 2.6 )
2.1Recommended Dosage for Primary Hemophagocytic Lymphohistiocytosis The recommended starting dose of GAMIFANT is 1 mg/kg given as a central or peripheral intravenous infusion over 1 hour twice per week (every three to four days). Doses subsequent to the initial dose may be increased based on clinical and laboratory criteria [see Dosage and Administration ( 2.5 )] . Administer GAMIFANT until hematopoietic stem cell transplantation (HSCT) is performed or unacceptable toxicity.
Discontinue GAMIFANT when a patient no longer requires therapy for the treatment of HLH.
2.2Recommended Dosage for Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome GAMIFANT is administered as a central or peripheral intravenous infusion over 1 hour according to the dosage schedule in Table 1. Doses may be increased based on clinical and laboratory criteria [see Dosage and Administration ( 2.6 )] . Discontinue GAMIFANT when a patient no longer requires therapy for the treatment of HLH/MAS.
Table 1. GAMIFANT Dosage in Patients with HLH/MAS Treatment Day GAMIFANT Dosage Day 1 6 mg/kg Days 4 to 16 3 mg/kg every 3 days for 5 doses From Day 19 onward 3 mg/kg twice per week (i.e., every 3 to 4 days)
2.3Monitoring to Assess Safety Before Initiating GAMIFANT Treatment Conduct testing for latent tuberculosis infections using the purified protein derivative (PPD) or IFNγ release assay and evaluate patients for tuberculosis risk factors prior to initiating GAMIFANT. Administer tuberculosis prophylaxis to patients at risk for tuberculosis, or known to have a positive PPD test result, or positive IFNγ release assay. During GAMIFANT Treatment Monitor for herpes zoster infection, adenovirus, EBV and CMV as clinically indicated.
2.4Prophylaxis and Concomitant Medication Information Prophylaxis Consider prophylaxis for herpes zoster, Pneumocystis jirovecii , and for fungal infections prior to GAMIFANT administration. Concomitant Medications For primary HLH patients who are not receiving baseline dexamethasone treatment, begin dexamethasone at a daily dose of at least 5 mg/m 2 to 10 mg/m 2 the day before GAMIFANT treatment begins. For patients who were receiving baseline dexamethasone, they may continue their regular dose provided the dose is at least 5 mg/m2.
Dexamethasone can be tapered according to the judgment of the treating physician [see Clinical Studies ( 14 )] .
2.5Dose Modification Based on Response for Primary Hemophagocytic Lymphohistiocytosis The GAMIFANT dose may be titrated up if disease response is unsatisfactory (see Table 2) [see Clinical Pharmacology ( 12.3 )] . After the patient's clinical condition is stabilized, decrease the dose to the previous level to maintain clinical response. Table 2: Dose Titration Criteria Treatment Day GAMIFANT Dose Criteria for Dose Increase Day 1 Starting Dose of 1 mg/kg N/A From Day 4 onwards Increase to 3 mg/kg Unsatisfactory improvement in clinical condition, as assessed by a healthcare provider AND at least one of the following: Fever - persistence or recurrence Platelet count If baseline < 50,000/mm 3 and no improvement to > 50,000/mm 3 If baseline > 50,000/mm 3 and less than 30% improvement If baseline > 100,000/mm 3 and decrease to < 100,000/mm 3 Neutrophil count If baseline < 500/mm 3 and no improvement to > 500/mm 3 If baseline > 500/mm 3 to 1,000/mm 3 and decrease to < 500/mm 3 If baseline 1,000/mm 3 to 1,500/mm 3 and decrease to < 1,000/mm 3 Ferritin (ng/mL) If baseline ≥3,000 ng/mL and < 20% decrease If baseline < 3,000 ng/mL and any increase to…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS GAMIFANT is a clear to slightly opalescent, colorless to slightly yellow preservative-free solution available as: Injection: • 10 mg/2 mL (5 mg/mL) in a single-dose vial • 50 mg/10 mL (5 mg/mL) in a single-dose vial • 100 mg/20 mL (5 mg/mL) in a single-dose vial • 50 mg/2 mL (25 mg/mL) in a single-dose vial • 100 mg/4 mL (25 mg/mL) in a single-dose vial • 250 mg/10 mL (25 mg/mL) in a single-dose vial • 500 mg/20 mL (25 mg/mL) in a single-dose vial Injection: • 10 mg/2 mL (5 mg/mL) solution in a single-dose vial ( 3 ) • 50 mg/10 mL (5 mg/mL) solution in a single-dose vial ( 3 ) • 100 mg/20 mL (5 mg/mL) solution in a single-dose vial ( 3 ) • 50 mg/2 mL (25 mg/mL) solution in a single-dose vial ( 3 ) • 100 mg/4 mL (25 mg/mL) solution in a single-dose vial ( 3 ) • 250 mg/10 mL (25 mg/mL) solution in a single-dose vial ( 3 ) • 500 mg/20 mL (25 mg/mL) solution in a single-dose vial ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Infections: Monitor patients for signs and symptoms and treat promptly. Test for latent tuberculosis. Consider administering prophylactic treatment against herpes zoster, Pneumocystis jirovecii and fungal infections.
( 5.1 ) Live Vaccines: Do not administer live or live attenuated vaccines to patients receiving GAMIFANT. ( 5.2 ) Infusion-Related Reactions: Monitor patients for infusion-related reactions. Interrupt infusion for infusion reactions and institute appropriate medical management.
( 5.3 )
5.1Infections GAMIFANT may increase the risk of fatal and serious infections to include specific pathogens favored by IFNγ neutralization, including mycobacteria, herpes zoster virus, and Histoplasma capsulatum . Do not administer GAMIFANT in patients with infections caused by these pathogens until appropriate treatment has been initiated. In patients with primary HLH receiving GAMIFANT in clinical trials, serious infections such as sepsis, pneumonia, bacteremia, disseminated histoplasmosis, necrotizing fasciitis, viral infections, and perforated appendicitis were observed in 32% of patients.
The reported infections were viral (41%), bacterial (35%), fungal (9%), and the pathogen was not identified in 15% of cases. In patients with HLH/MAS in Still’s disease receiving GAMIFANT in clinical trials, serious infections such as pneumonia, cytomegalovirus infection, cytomegalovirus infection reactivation, and sepsis were observed in 13% of patients. The reported infections were viral (44%), bacterial (13%), fungal (3%) and the pathogen was not identified in (13%) of patients.
In the GAMIFANT clinical trials, additional infections were reported in patients treated with GAMIFANT including herpes zoster (2.4%) and mycobacterial infections (2.4%). Evaluate patients for tuberculosis risk factors and test for latent infection (PPD testing, PCR, or IFNγ release assay) prior to initiating GAMIFANT. Administer tuberculosis prophylaxis to patients at risk for tuberculosis or known to have a positive purified protein derivative (PPD) test result [see Dosage and Administration ( 2.2 )] .
Consider prophylaxis for herpes zoster, Pneumocystis jirovecii ,and fungal infection to mitigate the risk to patients while receiving GAMIFANT [see Dosage and Administration ( 2.3 )] .Employ surveillance testing during treatment with GAMIFANT. Closely monitor patients receiving GAMIFANT for signs or symptoms of infection, promptly initiate a complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy.
5.2Increased Risk of Infection with Use of Live Vaccines Do not administer live or live attenuated vaccines to patients receiving GAMIFANT and for at least 4 weeks after the last dose of GAMIFANT. The safety of immunization with live vaccines during or following GAMIFANT therapy has not been studied.
5.3Infusion-Related Reactions Infusion-related reactions in patients with primary HLH, including drug eruption, pyrexia, rash, erythema, and hyperhidrosis, were reported with GAMIFANT treatment in 27% of patients. In one-third of these patients, the infusion-related reaction occurred during the first infusion. Infusion-related reactions in patients with HLH/MAS in Still’s disease, including pyrexia, headache, paresthesia, bone pain, pruritic rash, and peripheral coldness, were reported with GAMIFANT treatment in 13% of patients.
Infusion-related reactions were reported as mild in 8% of patients and as moderate in 5% of patients. Infusion-related reactions were defined as any event reported to have occurred within 24 hours after the start of infusion and assessed as related to GAMIFANT. In the GAMIFANT clinical trials, additional infusion-related reactions that were reported in less than 3% of patients treated with GAMIFANT included: malaise, sinus tachycardia, feeling hot, and acute respiratory failure.
Monitor patients for infusion-related reactions which can be severe. Interrupt the…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in the labeling: Infections [see Warnings and Precautions ( 5.1 )] Increased Risk of Infection with Use of Live Vaccines [see Warnings and Precautions ( 5.2 )] Infusion-Related Reactions [see Warnings and Precautions ( 5.3 )] In patients with primary HLH, the most common adverse reactions (≥ 20%) were: infections, hypertension, infusion-related reactions, and pyrexia. ( 6.1 ) In patients with HLH/MAS in Still’s disease, the most common adverse reactions (≥20%) were: viral infections, including cytomegalovirus infection or reactivation, and rash.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact 1-866-773-5274 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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. Primary HLH The safety data described in this section reflect exposure to GAMIFANT in which 34 patients with untreated primary HLH and previously treated patients with primary HLH ( NCT01818492 ) received GAMIFANT at a starting dose of 1 mg/kg every 3 days with dose increases up to 10 mg/kg [see Dosage and Administration ( 2.1 ) and Clinical Studies ( 14 )] .
The median duration of treatment with GAMIFANT was 59 days (range: 4 to 245 days) and the median cumulative dose was 25 mg/kg (range: 4 to 254 mg/kg). The median age of study population was 1 year (range: 0.1 to 13 years), 53% were female, and 65% were Caucasian. Serious adverse reactions were reported in 53% of patients.
The most common serious adverse reactions (≥3%) included infections, gastrointestinal hemorrhage, and multiple organ dysfunction. Fatal adverse reactions occurred in two (6%) of patients and included septic shock and gastrointestinal hemorrhage. Disseminated histoplasmosis led to drug discontinuation in one patient.
The most commonly reported adverse reactions (≥20%) were infections, hypertension, infusion-related reactions, and pyrexia. Adverse reactions reported in ≥10% of patients during treatment with GAMIFANT are presented in Table 4. Table 4 : Adverse Reactions Reported in 10% of Patients with Primary HLH Adverse Reactions GAMIFANT (%) (N = 34) Infections a 56 Hypertension b 41 Infusion-related reactions c 27 Pyrexia 24 Hypokalemia 15 Constipation 15 Rash 12 Abdominal pain 12 Cytomegalovirus infection 12 Diarrhea 12 Lymphocytosis 12 Cough 12 Irritability 12 Tachycardia 12 Tachypnea 12 a Includes viral, bacterial, fungal, and infections in which no pathogen was identified b Includes secondary hypertension c Includes events of drug eruption, pyrexia, rash, erythema, and hyperhidrosis Additional selected adverse reactions (all grades) that were reported in less than 10% of patients treated with GAMIFANT included: vomiting, acute kidney injury, asthenia, bradycardia, dyspnea, gastro-intestinal hemorrhage, epistaxis, and peripheral edema.
HLH/MAS The safety of GAMIFANT was evaluated in two open-label clinical studies in patients with HLH/MAS in Stills disease, including sJIA [see Clinical Studies ( 14.2 )] . The pooled safety data from these two studies included 39 patients who received an initial dose of 6 mg/kg followed by 3 mg/kg every 3 days until Day 16, and then twice weekly thereafter. The median duration of treatment with GAMIFANT was 29 days (range: 7 to 220 days) and the median cumulative dose was 33 mg/kg (range: 12 to 175 mg/kg).
Serious adverse reactions were reported in 12 patients (31%), with the most common serious adverse reaction being pneumonia (5%). Fatal adverse reactions occurred in two patients (5%) and included multiple organ dysfunction and circulatory shock. Pneumonia led to drug discontinuation in one patient (3%).
The most common adverse reactions (≥20%) were viral infections, including cytomegalovirus i…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS
7.1Effect of GAMIFANT on Cytochrome P450 Substrates The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (such as IFNγ) during chronic inflammation. By neutralizing IFNγ, use of GAMIFANT may normalize CYP450 activities which may reduce the efficacy of drugs that are CYP450 substrates due to increased metabolism. Upon initiation or discontinuation of concomitant GAMIFANT, monitor for reduced efficacy and adjust dosage of CYP450 substrate drugs as appropriate.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary There are no available data on GAMIFANT use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In an animal reproduction study, a murine surrogate anti-mouse IFNγ antibody administered to pregnant mice throughout gestation crossed the placental barrier, and no fetal harm was observed (see Data ) . The estimated 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. Data Animal Data In a mouse embryo-fetal development study, a murine surrogate anti-mouse IFNγ antibody was administered every 3-4 days throughout organogenesis and late gestation at doses of 0, 30, 75 or 150 mg/kg/occasion.
The surrogate antibody was detected in the plasma of all treated pregnant mice and their corresponding fetuses. No maternal toxicity occurred and there was no evidence of teratogenicity or effects on embryo-fetal survival or growth.
8.2Lactation Risk Summary There is no information regarding the presence of emapalumab-lzsg in human milk, the effects on the breastfed child, or the effects on milk production. Published data suggest that only limited amounts of therapeutic antibodies are found in breast milk and they do not enter the neonatal and infant circulations in substantial amounts. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for GAMIFANT and any potential adverse effects on the breastfed child from GAMIFANT or from the underlying maternal condition.
8.4Pediatric Use Safety and effectiveness of GAMIFANT have been established in pediatric patients with primary HLH that is reactivated or refractory to conventional therapies and with HLH/MAS in Still’s Disease (including sJIA) with an inadequate response to glucocorticoids [see Clinical Studies ( 14 )]. Use of GAMIFANT is supported by 3 single-arm trials which included 57 pediatric patients: 27 with primary HLH and 30 with HLH/MAS in Still’s disease. These studies included pediatric patients in the following age groups: 5 patients newborn to 6 months, 13 patients 6 months to 2 years, 27 patients from 2 years to <12 years, and 12 patients from 12 years to <17 years.
8.5Geriatric Use Clinical studies of GAMIFANT did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no available data on GAMIFANT use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In an animal reproduction study, a murine surrogate anti-mouse IFNγ antibody administered to pregnant mice throughout gestation crossed the placental barrier, and no fetal harm was observed (see Data ) . The estimated 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. Data Animal Data In a mouse embryo-fetal development study, a murine surrogate anti-mouse IFNγ antibody was administered every 3-4 days throughout organogenesis and late gestation at doses of 0, 30, 75 or 150 mg/kg/occasion.
The surrogate antibody was detected in the plasma of all treated pregnant mice and their corresponding fetuses. No maternal toxicity occurred and there was no evidence of teratogenicity or effects on embryo-fetal survival or growth.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of GAMIFANT have been established in pediatric patients with primary HLH that is reactivated or refractory to conventional therapies and with HLH/MAS in Still’s Disease (including sJIA) with an inadequate response to glucocorticoids [see Clinical Studies ( 14 )]. Use of GAMIFANT is supported by 3 single-arm trials which included 57 pediatric patients: 27 with primary HLH and 30 with HLH/MAS in Still’s disease. These studies included pediatric patients in the following age groups: 5 patients newborn to 6 months, 13 patients 6 months to 2 years, 27 patients from 2 years to <12 years, and 12 patients from 12 years to <17 years.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of GAMIFANT did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
🆘 Overdosage ▾
10 OVERDOSAGE Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Emapalumab-lzsg is a monoclonal antibody that binds to and neutralizes interferon gamma (IFNγ). Nonclinical data suggest that IFNγ plays a pivotal role in the pathogenesis of HLH by being hypersecreted.
12.2Pharmacodynamics IFNγ Inhibition Emapalumab-lzsg reduces the plasma concentrations of CXCL9, a chemokine induced by IFNγ. Cardiac Electrophysiology At a dose of 3 mg/kg GAMIFANT does not prolong the QT interval to any clinically relevant extent.
12.3Pharmacokinetics The pharmacokinetics of emapalumab-lzsg were evaluated in healthy adult subjects and in patients with HLH. Following a 1 mg/kg emapalumab-lzsg dose, median steady state peak concentration was 44 mcg/mL, which was 2.9 times higher than after the first dose. The median steady state trough concentration was 25 mcg/mL, which was 4.3 times higher than after the first dose.
Emapalumab-lzsg AUC increases slightly more than proportionally between 1 and 3 mg/kg doses, and less than proportionally at 3, 6, and 10 mg/kg doses. Emapalumab-lzsg exhibits target-mediated-like clearance dependent on IFNγ production, which can vary between and within patients as a function of time and can affect the recommended dosage [see Dosage and Administration ( 2.2 )] . Emapalumab-lzsg steady state is achieved by the 7th infusion when the IFNγ production is moderate.
At high IFNγ production, steady-state is reached earlier due to a shorter half-life. Distribution The central and peripheral volumes of distribution in a subject with body weight of 70 kg are 2.8 and
4.4L, respectively. Elimination Emapalumab-lzsg elimination half-life is approximately 22 days in healthy subjects and ranged from 2.5 to 18.9 days in HLH patients. In patients with HLH, the elimination half-life of emapalumab-lzsg was significantly influenced by the amount of IFNγ within the patient, demonstrating a target mediated clearance-like mechanism.
The elimination half-life of emapalumab-lzsg is reduced as the concentration of IFNγ increases. Emapalumab-lzsg clearance is approximately 0.007 L/h in healthy subjects. Metabolism The metabolic pathway of emapalumab-lzsg has not been characterized.
Like other protein therapeutics, GAMIFANT is expected to be degraded into small peptides and amino acids via catabolic pathways. Specific Populations Body weight (3 to 80 kg) was a significant covariate of emapalumab-lzsg pharmacokinetics, supporting body weight-based dosing. No clinically significant differences in the pharmacokinetics of emapalumab-lzsg were observed based on age (0.02 to 64 year), sex (53% Females), race (71.4% Caucasian, 12.2% Asian and 8.2% Black), renal impairment including dialysis, or hepatic impairment (mild, moderate, and severe).
Drug Interaction Studies No drug-drug interaction studies have been conducted with GAMIFANT.
12.4Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other emapalumab products may be misleading. The immunogenicity of emapalumab-lzsg has been evaluated using an electrochemiluminescence-based immunoassay (ECLIA). Treatment-emergent anti-drug antibodies (ADAs) were detected in 1/33 (3%) of patients in the primary HLH clinical trial.
The ADAs in this patient were found to have neutralizing ability. Treatment-emergent ADAs were detected in 5/35 patients (14%) in the two HLH/MAS clinical trials. None of the ADAs in these 5 patients were found to have neutralizing ability.
No evidence of…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Emapalumab-lzsg is a monoclonal antibody that binds to and neutralizes interferon gamma (IFNγ). Nonclinical data suggest that IFNγ plays a pivotal role in the pathogenesis of HLH by being hypersecreted.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING GAMIFANT (emapalumab-lzsg) injection is a sterile, clear to slightly opalescent, colorless to slightly yellow solution supplied in the following packaging configuration: NDC 66658-501-01 – containing one 10 mg/2 mL (5 mg/mL) single-dose vial NDC 66658-505-01 – containing one 50 mg/10 mL (5 mg/mL) single-dose vial NDC 66658-510-01 – containing one 100 mg/20 mL (5 mg/mL) single-dose vial NDC 66658-522-01 – containing one 50 mg/2 mL (25 mg/mL) single-dose vial NDC 66658-523-01 – containing one 100 mg/4 mL (25 mg/mL) single-dose vial NDC 66658-524-01 – containing one 250 mg/10 mL (25 mg/mL) single-dose vial NDC 66658-525-01 – containing one 500 mg/20 mL (25 mg/mL) single-dose vial Store GAMIFANT in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF) in original carton to protect from light.
Do not freeze or shake. This product contains no preservative.
📋 Description ▾
11 DESCRIPTION Emapalumab-lzsg is an interferon gamma (IFNγ) neutralizing antibody. Emapalumab-lzsg is produced in Chinese Hamster Ovary cells by recombinant DNA technology. Emapalumab-lzsg is an IgG1 immunoglobulin with a molecular weight of approximately 148 kDa.
GAMIFANT (emapalumab-lzsg) injection for intravenous use is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution provided in single-dose vials that require dilution prior to intravenous infusion. GAMIFANT 5 mg/mL (2 mL, 10 mL and 20 mL) Each vial contains 10 mg/2 mL, 50 mg/10 mL, or 100 mg/20 mL emapalumab-lzsg at a concentration of 5 mg/mL. Each mL also contains the following inactive ingredients: L-Histidine (1.55 mg), L-Histidine monohydrochloride, monohydrate (3.14 mg), Polysorbate 80 (0.05 mg), sodium chloride (7.30 mg), and Water for Injection, USP.
GAMIFANT 25 mg/mL (2 mL, 4 mL, 10 mL and 20 mL) Each vial contains 50 mg/2 mL, 100 mg/4 mL, 250 mg/10 mL or 500 mg/20 mL emapalumab- lzsg at a concentration of 25 mg/mL. Each mL also contains the following inactive ingredients: L-Histidine (1.55 mg), L-Histidine monohydrochloride, monohydrate (3.14 mg), Polysorbate 80 (0.05 mg), sodium chloride (7.30 mg), and Water for Injection, USP.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Infections Inform patients and their caregivers of the risk of developing infections during treatment with GAMIFANT, and to report any symptoms of infection [see Warnings and Precautions ( 5.1 )] . Vaccinations Advise patients and their caregivers that the patient should not receive live or live attenuated vaccines during GAMIFANT treatment [see Warnings and Precautions ( 5.2 )] .
Infusion-Related Reactions Advise patients and their caregivers of the potential for developing infusion-related reactions during treatment with GAMIFANT [see Warnings and Precautions ( 5.3 )] . Manufactured by: Swedish Orphan Biovitrum AB (publ) Stockholm, Sweden U.S. License Number 1859 Distributed by: Sobi Inc.
77 Fourth Avenue, 3 rd Floor Waltham, MA 02451-7559 Manufactured at: Patheon Italia S.p.A 2° Trav. SX Via Morolense, 5 03013-Ferentino Italy Product of the United Kingdom
💬 Medication Guide ▾
MEDICATION GUIDE GAMIFANT ® (gam i fant) (emapalumab-lzsg) injection, for intravenous use What is the most important information I should know about GAMIFANT? GAMIFANT can cause serious side effects including: Infections. GAMIFANT is a medicine that affects your immune system and may lower the ability of your immune system to fight infections.
GAMIFANT may increase your risk of serious infections that can lead to death. These infections include tuberculosis (TB), histoplasmosis, pneumonia, cytomegalovirus infection or reactivation of infection, sepsis, herpes zoster infection (shingles) and other infections caused by viruses, fungi or bacteria that can spread throughout the body. Your healthcare provider will: test you for TB before you start treatment with GAMIFANT. treat you with a medicine for TB if you are at risk for TB or if you have a known positive TB test.
Infections are common in people treated with GAMIFANT. Before starting GAMIFANT, tell your healthcare provider if you: had TB in the past, or if you or a member of your family have been in recent close contact with someone with TB. have ever had a positive TB skin test (PPD). currently have or have had history of infections, including histoplasmosis, cytomegalovirus, or herpes zoster (shingles). are being treated for an active infection. have symptoms of an infection, such as fever, sweat and chills, cough, breathing problems, blood in mucus (phlegm), warm, red, or painful skin or sores on your body.
Your healthcare provider may give you medicine to help prevent certain infections before you receive GAMIFANT. After starting GAMIFANT , tell your healthcare provider if: new symptoms of an infection appear. symptoms of an infection that you already had when starting GAMIFANT worsen. Your healthcare provider will monitor you closely for signs and symptoms of infections during treatment with GAMIFANT.
See " What are the possible side effects of GAMIFANT? " for more information about side effects. What is GAMIFANT? GAMIFANT is a prescription medicine used for the treatment of hemophagocytic lymphohistiocytosis (HLH) in adults and children with: primary HLH whose disease has come back or progressed, or other medicines have not worked well enough or cannot be tolerated.
HLH/macrophage activation syndrome (MAS) in known or suspected Still's disease, including systemic Juvenile Idiopathic Arthritis (sJIA), when glucocorticoids have not worked well enough or cannot be tolerated, or with MAS that has come back. Before you receive GAMIFANT, tell your healthcare provider about all of your medical conditions including if you: have an infection (see What is the most important information I should know about GAMIFANT? ) have received or are scheduled to receive an immunization (vaccine). You should not receive "live or live attenuated" vaccines during your treatment with GAMIFANT and for at least 4 weeks after the last dose of GAMIFANT. are pregnant or plan to become pregnant.
It is not known if GAMIFANT can harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if GAMIFANT passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with GAMIFANT.
Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. How will I receive GAMIFANT? You will receive GAMIFANT through a vein by intravenous (IV) infusion over 1 hour.
Your healthcare provider will monitor you during the infusion for side effects. For primary HLH: o GAMIFANT is given 2 times a week (every 3 to 4 days). o GAMIFANT is used with another prescription medicine called dexamethasone. You can ask your healthcare provider for information about dexamethasone.
For HLH/MAS in Still's disease, after your first dose, GAMIFANT is given every 3 days for 5 doses, then 2 times a week (every 3 to 4 days). Your healthcare provider will do blood tests during your tre…