Gamifant
(emapalumab-lzsg)Dosage & Administration
For intravenous infusion only:
• Recommended starting dosage: 1 mg/kg as an intravenous infusion over 1 hour twice per week. ( 2.1)
• Administer dexamethasone concomitantly with GAMIFANT. ( 2.3)
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Gamifant Prescribing Information
GAMIFANT is indicated for the treatment of adult and pediatric (newborn and older) patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy.
Recommended Dosing
The recommended starting dose of GAMIFANT is 1 mg/kg given as an 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 ( 2.4)] .
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.
Monitoring 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 tuberculosis, adenovirus, EBV and CMV every 2 weeks and as clinically indicated.
Pre-Medications and Concomitant Medication Information
Pre-Medications
Administer prophylaxis for Herpes Zoster, Pneumocystis jirovecii, and for fungal infections prior to GAMIFANT administration.
Concomitant Medications
For patients who are not receiving baseline dexamethasone treatment, begin dexamethasone at a daily dose of at least 5 to 10 mg/m 2the 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/m 2. Dexamethasone can be tapered according to the judgment of the treating physician [see Clinical Studies ( 14)] .
Dose Modification Based on Response
The GAMIFANT dose may be titrated up if disease response is unsatisfactory (see Table 1) [see Clinical Pharmacology ( 12.3)] . After the patient's clinical condition is stabilized, decrease the dose to the previous level to maintain clinical response.
| Treatment Day | GAMIFANT Dose | Criteria for Dose Increase |
| Day 1 | Starting Dose of 1 mg/kg | N/A |
| On Day 3 | Increase to 3 mg/kg | Unsatisfactory improvement in clinical condition, as assessed by a healthcare provider AND at least one of the following:
|
| From Day 6 onwards | Increase to 6 mg/kg | |
| From Day 9 onwards | Increase to 10 mg/kg | Assessment by a healthcare provider that based on initial signs of response, a further increase in GAMIFANT dose can be of benefit |
Instructions for Preparation and Administration
Preparation
GAMIFANT vials are for single-use only.
Do not mix GAMIFANT 5 mg/mL and 25 mg/mL vials together.
Prepare the solution for infusion as follows:
- Calculate the dose (mg/kg), total volume (mL) of GAMIFANT required and the number of GAMIFANT vials needed based on patient actual body weight [see Dosage and Administration ( 2.1)] .
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. GAMIFANT is a clear to slightly opalescent, colorless to slightly yellow liquid. Do not administer if discolored or foreign particulate matter is present.
- Withdraw the necessary amount of GAMIFANT solution and dilute with 0.9% Sodium Chloride Injection, USP.
- For GAMIFANT 5 mg/mL vials:
- Dilute to a maximum concentration of 2.5 mg/mL. Do not dilute product to less than 0.25 mg/mL.
- The diluted solution can be placed in either a syringe or an infusion bag, depending on the volume needed.
- When using a syringe, use a gamma irradiated or ethylene oxide sterilized latex-free, polyvinyl chloride (PVC)-free syringe.
- When using an infusion bag, use a non-PVC polyolefin infusion bag.
- For GAMIFANT 25 mg/mL vials:
- Dilute to a maximum concentration of 12.5 mg/mL. Do not dilute product to less than 1.25 mg/mL.
- Use a non-PVC polyolefin infusion bag made from either polyethylene or ethylene/propylene copolymer.
- For GAMIFANT 5 mg/mL vials:
- Discard any unused portion left in the vial(s).
Administration
- Administer GAMIFANT diluted solution intravenously over 1 hour through an intravenous line containing a sterile, non-pyrogenic, low-protein binding 0.2 micron in-line filter.
- Do not infuse GAMIFANT concomitantly with other agents and do not add any other product to the infusion bag or syringe.
- Do not store any unused portion of the infusion solution for reuse. Any unused product or waste material should be disposed of in accordance with local requirements.
Storage of Diluted Solution
This product does not contain a preservative.
If not administered immediately:
- Store the diluted solution of GAMIFANT under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 4 hours from the time of dilution.
- If refrigerated, allow the diluted solution to come to room temperature prior to administration.
- Do not freeze. Do not shake.
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
Pregnancy
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.
Lactation
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.
Pediatric Use
Safety and effectiveness of GAMIFANT have been established in pediatric patients, newborn and older, with primary HLH that is reactivated or refractory to conventional therapies. Use of GAMIFANT is supported by a single-arm trial in 27 pediatric patients with reactivated or refractory primary HLH. This study included pediatric patients in the following age groups: 5 patients newborn to 6 months, 10 patients 6 months to 2 years, and 12 patients from 2 years to 13 years [see Clinical Studies ( 14)] .
Geriatric 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.
None.
Infections
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 32% of patients receiving GAMIFANT in clinical trials, serious infections such as sepsis, pneumonia, bacteremia, disseminated histoplasmosis, necrotizing fasciitis, viral infections, and perforated appendicitis were observed. The reported infections were viral (41%), bacterial (35%), fungal (9%), and the pathogen was not identified in 15% of cases.
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)] .
Administer prophylaxis for Herpes Zoster, Pneumocystis jirovecii, and fungal infection to mitigate the risk to patients while receiving GAMIFANT. 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.
Increased 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.
Infusion-Related Reactions
Infusion-related reactions 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.
All infusion related reactions were reported as mild to moderate. Monitor patients for infusion- related reactions. Interrupt infusion for infusion reactions and institute appropriate medical management prior to continuing infusion at a slower rate.