Trogarzo
(ibalizumab-uiyk)Dosage & Administration
The recommended dosage regimen is a single loading dose of 2,000 mg followed by a maintenance dose of 800 mg every 2 weeks administered as a diluted intravenous infusion (IV infusion) or undiluted intravenous push (IV push). ( 2.1, 2.2, 2.3)
Duration of IV Infusion or IV Push
| IV Infusion (Diluted) | IV Push (Undiluted) | |
| Loading Dose 2,000 mg | Over at least 30 minutes | Over at least 90 seconds |
| Maintenance Dose 800 mg | Over at least 15 minutes | Over at least 30 seconds |
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Trogarzo Prescribing Information
TROGARZO, in combination with other antiretroviral(s), is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen.
Recommended Dosage
The recommended dosage regimen is a single loading dose of 2,000 mg followed by a maintenance dose of 800 mg every 2 weeks administered as a diluted intravenous infusion (IV infusion) or undiluted intravenous push (IV push) [see Dosage and Administration ]. TROGARZO is available in a single-dose, 2 mL vial containing 150 mg/mL of ibalizumab-uiyk. Each vial delivers approximately 1.33 mL containing 200 mg of ibalizumab-uiyk. Dose modifications of TROGARZO are not required when administered with any other antiretroviral or any other treatments.
Preparation
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard vial if solution is cloudy, if there is pronounced discoloration or if there is foreign particulate matter.
See Table 1 for the appropriate number of vials required to prepare both the loading dose of 2,000 mg and the maintenance doses of 800 mg.
| TROGARZO Dose | TROGARZO Vials (Total Volume to be Withdrawn) |
Loading dose of 2,000 mg (IV infusion or undiluted IV push) | 10 vials (13.3 mL) |
Maintenance dose of 800 mg (IV infusion or undiluted IV push) | 4 vials (5.32 mL) |
TROGARZO solution for IV infusion or IV push should be prepared by a trained medical professional using aseptic technique as follows:
For intravenous infusion
For administration as an IV infusion, the appropriate number of vials are diluted in 250 mL of 0.9% Sodium Chloride Injection, USP.
• Remove the flip-off cap from the single-dose vial and wipe the stopper with an alcohol swab.
• Insert sterile syringe needle into the vial through the center of the stopper and withdraw 1.33 mL from each vial (NOTE: a small residual amount may remain in the vial, discard unused portion) and transfer into a 250 mL intravenous bag of 0.9% Sodium Chloride Injection, USP. Other intravenous diluents must not be used to prepare the TROGARZO solution for infusion.
• Once diluted, the TROGARZO solution should be administered immediately.
• If not administered immediately, store the diluted TROGARZO solution at room temperature (20°C to 25°C, 68°F to 77°F) for up to 4 hours, or refrigerated (2°C to 8°C, 36°F to 46°F) for up to 24 hours. If refrigerated, allow the diluted TROGARZO solution to stand at room temperature (20°C to 25°C, 68°F to 77°F) for at least 30 minutes but no more than 4 hours prior to administration.
• Discard partially used vials or empty vials of TROGARZO and any unused portion of the diluted TROGARZO solution.
For intravenous push
For administration as an IV push, undiluted TROGARZO solution is administered.
• Allow the vials to stand at room temperature for approximately 5 minutes.
• Remove the flip-off cap from the single-dose vial and wipe the stopper with an alcohol swab.
• Insert sterile syringe needle into the vial through the center of the stopper and withdraw 1.33 mL from each vial (NOTE: a small residual amount may remain in the vial, discard unused portion).
• The undiluted TROGARZO solution should be administered immediately.
• Discard partially used vials or empty vials of TROGARZO and any unused portion of the undiluted TROGARZO solution.
Administration
TROGARZO solution should be administered by a trained medical professional.
Administer TROGARZO intravenously (as an IV infusion or IV push) in the cephalic vein of the patients right or left arm. If this vein is not accessible, an appropriate vein located elsewhere can be used. Table 2 outlines the duration of IV infusion or IV push for the loading dose and maintenance dose.
| IV Infusion (Diluted) | IV Push (Undiluted) | |
| Loading Dose 2,000 mg | Over at least 30 minutes | Over at least 90 seconds |
| Maintenance Dose 800 mg | Over at least 15 minutes | Over at least 30 seconds |
After the IV infusion is complete, flush with 30 mL of 0.9% Sodium Chloride Injection, USP.
After the IV push is complete, flush with 2 to 5 mL of 0.9% Sodium Chloride Injection, USP.
All patients must be observed for 1 hour after completion of TROGARZO loading dose as an IV infusion or IV push. If the patient does not experience an infusion-associated adverse reaction, the post-administration observation time for the subsequent maintenance doses (IV infusion or IV push) can be reduced to 15 minutes.
If a maintenance dose (800 mg) of TROGARZO is missed by 3 days or longer beyond the scheduled dosing day, a loading dose (2,000 mg) should be administered as early as possible. Resume maintenance dosing (800 mg) every 14 days thereafter.
Injection: 200 mg/1.33 mL (150 mg/mL) colorless to slightly yellow and clear to slightly opalescent solution with no visible particles in a single-dose vial.
Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiretrovirals during pregnancy. This registry does not include Trogarzo, but likely includes patients’ concomitant antiretroviral drugs. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1–800–258–4263.
Risk Summary
Based on animal data, ibalizumab-uiyk use during pregnancy may cause reversible immunosuppression (CD4+ T cell and B cell lymphocytopenia) in infants exposed to ibalizumab-uiyk in utero. Immunoglobulin G (IgG) antibodies, such as ibalizumab-uiyk, are transported across the placenta in significant amounts, especially near term; therefore, ibalizumab-uiyk has the potential to be transferred from the mother to the developing fetus (see Clinical Considerations). There are no available data on ibalizumab-uiyk use in pregnant women to evaluate for a drug- associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. 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 2-4% and 15-20%, respectively.
In a reproductive study in monkeys, reversible decreases in CD4+ T cells and B cells and increases in CD8+ T cells were observed within the first 4 weeks after birth in infants born to pregnant monkeys receiving ibalizumab-uiyk intravenously (see Data). Lymphocyte counts returned to near normal levels by 3 months of age. One infant monkey died from a systemic viral infection that may be related to ibalizumab-uiyk-induced immunosuppression. No malformations or premature births were observed in this study.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
Immunoglobulin G (IgG) antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. Administration of TROGARZO during pregnancy may affect immune responses in the in utero-exposed infant. For infants with perinatal exposure to TROGARZO, immune phenotyping of the peripheral blood, including CD4+ T cell and B cell counts, is recommended. Expert consultation is also recommended to provide guidance on monitoring and management (e.g., need for antibiotic or immunoprophylaxis) of exposed infants based on the degree of immunosuppression observed. The safety of administering live or live-attenuated vaccines in exposed infants is unknown.
Data
Animal Data
In an enhanced pre- and post-natal development (ePPND) study, pregnant cynomolgus monkeys were administered intravenous doses of either vehicle or 110 mg/kg ibalizumab-uiyk every week from Gestation Day 20-22 (GD 20-22) until parturition on GD 160 ± 10. Significant changes in infant monkey immune cell levels on Postnatal Day (PND) 14 (mean decreases of 78% in CD4+ T cells and 46% in B cells and increases of 2.3-fold in CD8+ T cells) and PND 28 (mean decreases of 73% in CD4+ T cells and increases of 2.2-fold in CD8+ T cells), attributed to in utero ibalizumab-uiyk exposure, were observed relative to concurrent controls. The lymphocyte changes correlated with infant ibalizumab-uiyk serum concentrations and appeared to return to near normal levels between PND 28-91, when ibalizumab-uiyk concentrations were nearly undetectable. Although ibalizumab-uiyk exposure in these infant monkeys may be significantly higher than in human infants following in utero exposure at the recommended human maintenance dose, the risk of ibalizumab-uiyk-induced immunosuppression in human infants is possible. No meaningful differences in infant monkey lymphocyte counts were observed on PND 180. Further, no differences in immune cell function were observed in a T cell-dependent response assay conducted on PND 138 to 180 ± 2 following immunization of the infant monkeys with keyhole limpet hemocyanin. One treatment-group infant monkey died on PND 24 from a systemic viral infection with secondary superficial bacterial infection which was acquired during the postnatal period. Despite the low incidence (1 of 20 infants), the death may be related to ibalizumab-uiyk-induced immunosuppression. Decreases in CD4+ T cells (93%), and B cells (92%) were observed in this infant on PND 14, and decreased cellularity was observed in the spleen, thymus and mandibular lymph node. Unlike the rest of the ibalizumab-exposed infant monkey population, this infant also exhibited a decrease in CD8+ T cells of 71% on PND 14. Body weight was also decreased in this infant between PND 14 and 24. No structural abnormalities were observed among the ibalizumab-uiyk-exposed infants. In addition, no maternal toxicities, including no changes in maternal lymphocyte subsets or effects on embryo-fetal survival, were observed.
Lactation
Risk Summary
The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers in the United States not breastfeed their infants to avoid the risk of postnatal transmission of HIV-1 infection.
No data are available regarding the presence of TROGARZO in human milk, the effects on the breastfed child, or the effects on milk production. Human IgG is present in human milk, although published data indicate that antibodies in breast milk do not enter the neonatal or infant circulation system in substantial amounts. Because of the potential for HIV-1 transmission, instruct mothers not to breastfeed if they are receiving TROGARZO.
Pediatric Use
The safety and effectiveness of TROGARZO in pediatric patients have not been established.
Geriatric Use
No studies have been conducted with TROGARZO in geriatric patients.
TROGARZO is contraindicated in patients with a prior hypersensitivity reaction to TROGARZO or any components of the product [see Warnings and Precautions ].
Hypersensitivity Including Infusion-Related and Anaphylactic Reactions
Hypersensitivity reactions including infusion-related reactions and anaphylactic reactions have been reported following infusion of TROGARZO during post-approval use. Symptoms may include dyspnea, angioedema, wheezing, chest pain, chest tightness, cough, hot flush, nausea, and vomiting. If signs and symptoms of an anaphylactic or other clinically significant hypersensitivity reaction occur, immediately discontinue administration of TROGARZO and initiate appropriate treatment. The use of TROGARZO is contraindicated in patients with known hypersensitivity with TROGARZO [see Contraindications ( 4), Adverse Reactions ( 6.2)].
Immune Reconstitution Inflammatory Syndrome
Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment.
Embryo-Fetal Toxicity
Based on animal data, TROGARZO may cause reversible immunosuppression (CD4+ T cell and B cell lymphocytopenia) in infants born to mothers exposed to TROGARZO during pregnancy. Immune phenotyping of the peripheral blood and expert consultation are recommended to provide guidance regarding monitoring and management of exposed infants based on the degree of immunosuppression observed. The safety of administering live or live-attenuated vaccines in exposed infants is unknown. [see Use In Specific Populations ( 8.1)]