Ibalizumab is an intravenous recombinant humanized monoclonal antibody indicated for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug resistant HIV-infection failing other therapies. Ibalizumab is the first drug in a new class of antiretrovirals that can provide significant benefit to patients who have failed several other antiretrovirals and who have run out of treatment options. In clinical studies of patients with viral load more than 1,000 copies/mL and documented resistance to at least 1 antiretroviral medication from each of 3 classes (NRTI, NNRTI, and PI), 83% of patients met the primary endpoint, achieving at least a 0.5 log10 decrease in viral load at the end of the functional monotherapy period compared with 3% of patients at the end of the control period. At week 25, 43% and 50% of patients, respectively, achieved a viral load less than 50 copies/mL and HIV-1 RNA less than 200 copies/mL. The mean and median CD4 count increased by 44 cells/mm3 and 17 cells/mm3, respectively, from baseline to week 25. Ibalizumab is given as a single IV loading dose, followed by a maintenance dose every 2 weeks.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Administer intravenously (IV) as a diluted IV infusion or undiluted as an IV push.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Ibalizumab is a colorless to slightly yellow and clear to slightly opalescent solution with no visible particles. Discard a vial if the solution is cloudy, if there is pronounced discoloration, or if there is foreign particulate matter.
Intravenous Administration
Dilution for IV Infusion:
-IV infusions should be prepared by a trained medical professional using aseptic technique.
-Select the appropriate number of vials necessary for either the loading dose (10 vials) or maintenance dose (4 vials).
-Withdraw 1.33 mL from each vial and transfer into a 250 mL IV bag of 0.9% Sodium Chloride for Injection. Do not use other diluents.
-Once diluted, the solution should be administered immediately.
-Storage: The diluted solution may be stored at room temperature (20 to 25 degrees C or 68 to 77 degrees F) for up to 4 hours or refrigerated (2 to 8 degrees C or 36 to 46 degrees F) for up to 24 hours. If refrigerated, allow the diluted solution to stand at room temperature for at least 30 minutes, but no more than 4 hours prior to administration.
-Discard partially used or empty vials and any unused portion of the diluted solution.
Intermittent IV Infusion Administration:
-IV infusions should be administered by a trained medical professional.
-Administer the infusion in the cephalic vein of the patient's arm or an appropriate vein located elsewhere.
-Infuse the loading dose (2,000 mg) over no less than 30 minutes. The infusion rate for subsequent maintenance doses (800 mg) can be decreased to no less than 15 minutes.
-Flush with 30 mL of 0.9% Sodium Chloride for Injection after the completion of each infusion.
-All patients must be observed for 1 hour after completion of ibalizumab administration for at least the first infusion. If there are no infusion-associated adverse reactions, subsequent observation time can be reduced to 15 minutes.
Preparation for IV Push:
-The IV push should be prepared by a trained medical professional using aseptic technique.
-Allow 10 vials (loading dose) or 4 vials (maintenance dose) to stand at room temperature for approximately 5 minutes.
-Using a sterile syringe and needle, withdraw 1.33 mL from each vial for a total dose volume of 13.3 mL (loading dose) or 5.32 mL (maintenance dose).
-The undiluted solution should be administered immediately.
-Discard partially used or empty vials and any unused portion of the undiluted solution.
IV Push Administration:
-The IV push should be administered by a trained medical professional.
-Administer the undiluted IV push over a 90-second period (loading dose) or 30-second period (maintenance dose) in the cephalic vein of the patient's arm or an appropriate vein located elsewhere.
-Flush with 2 to 5 mL of 0.9% Sodium Chloride for Injection after the completion of each IV push.
-Observe patients for 1 hour after each dose. However, the post-administration observation time for maintenance IV pushes can be reduced to 15 minutes if no infusion-associated adverse reactions occurred with the loading dose.
Missed Doses:
-If a maintenance dose (800 mg) 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.
During a clinical trial (n = 40) of patients who received ibalizumab with optimized background therapy, diarrhea and nausea were reported in 8% and 5% of patients, respectively.
Dizziness was reported in 8% of patients who received ibalizumab with optimized background therapy during a clinical trial (n = 40).
Rash, including generalized rash, erythematous rash, maculopapular rash, and papular rash, was reported in 5% of patients who received ibalizumab with optimized background therapy during a clinical trial (n = 40). Most adverse reactions were mild to moderate in severity; however, 1 patient developed a severe rash. During postmarketing use of the drug, cases of pruritus have been reported. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
As with all therapeutic proteins, there is a potential for immunogenicity with ibalizumab. Anti-ibalizumab antibody formation occurred in 1 patient receiving ibalizumab in clinical trials; no adverse reaction or reduced efficacy was attributed to the positive sample in this patient.
Immune reconstitution syndrome, manifested as an exacerbation of progressive multifocal leukoencephalopathy, was reported in 1 patient who received ibalizumab with optimized background therapy during a clinical trial (n = 40).
Laboratory abnormalities reported in a clinical trial (n = 40) of patients receiving ibalizumab with optimized background therapy included hyperbilirubinemia (5%; bilirubin of 2.6 or more times the upper limit of normal [ULN]); increased direct bilirubin (3%; more than ULN), increased creatinine (10%; more than 1.8 times the ULN or 1.5 times baseline), hyperglycemia (3%; blood glucose more than 250 mg/dL), increased lipase (5%; more than 3 times the ULN), increased uric acid (3%; more than 12 mg/dL), decreased hemoglobin (3%; less than 8.5 g/dL), thrombocytopenia (3%; platelets less than 50,000 cells/mm3), decreased leukocytes (5%; less than 1,500 cells/mm3), and neutropenia (5%; less than 600 cells/mm3).
Hypersensitivity reactions, including infusion-related reactions and anaphylactoid reactions, have been reported during postmarketing use of ibalizumab. Symptoms associated with these reactions have included angioedema, chest pain, chest tightness, cough, dyspnea, hot flush, nausea, vomiting, and wheezing. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
During baseline evaluation of people with HIV, discuss risk reduction measures and the need for status disclosure to sexual or needle-sharing partners, especially with untreated patients who are still at high risk of HIV transmission. Include the importance of adherence to therapy to achieve and maintain a plasma HIV RNA less than 200 copies/mL. Maintaining a plasma HIV RNA less than 200 copies/mL, including any measurable value below this threshold, with antiretroviral therapy prevents sexual transmission of HIV to their partners. Patients may recognize this concept as Undetectable = Untransmittable or U=U. Instruct patients to achieve sustained viral suppression (i.e., 2 recorded measurements of plasma viral loads that are below the limits of detection and taken at least 3 months apart) before attempting to conceive a child in order to maximize their health, prevent HIV sexual transmission, and minimize the risk of HIV transmission to the infant once conception occurs. For partners with different HIV status when the person with HIV is on antiretroviral therapy and has achieved sustained viral suppression, sexual intercourse without a condom allows conception without sexual HIV transmission to the person without HIV. Expert consultation is recommended.
Unplanned antiretroviral therapy interruption may be necessary for specific situations, such as serious drug toxicity, intercurrent illness or surgery precluding oral intake (e.g., gastroenteritis or pancreatitis), severe hyperemesis gravidarum unresponsive to antiemetics, or drug non-availability. If short-term treatment interruption (i.e., less than 1 to 2 days) is necessary, in general, it is recommended that all antiretroviral agents be discontinued simultaneously, especially if the interruption occurs in a pregnant patient or is because of a serious toxicity. However, if a short-term treatment interruption is anticipated in the case of elective surgery, the pharmacokinetic properties and food requirements of specific drugs should be considered; as stopping all simultaneously in a regimen containing drugs with differing half-lives may result in functional monotherapy of the drug with the longest half-life and may increase the risk for resistant mutations. Healthcare providers are advised to reinitiate a complete and effective antiretroviral regimen as soon as possible after an interruption of therapy. Planned long-term treatment interruptions are not recommended due to the potential for HIV disease progression (i.e., declining CD4 counts, viral rebound, acute viral syndrome), development of minor HIV-associated manifestations or serious non-AIDS complications, development of drug resistance, increased risk of HIV transmission, and increased risk for opportunistic infections. If therapy must be discontinued, counsel patient on the potential risks and closely monitor for any clinical or laboratory abnormalities.
Immune reconstitution syndrome has been reported in patients treated with ibalizumab in combination with other antiretrovirals. During the initial phase of HIV treatment, patients whose immune system responds to ibalizumab therapy may develop an inflammatory response to indolent or residual opportunistic infections (such as progressive multifocal leukoencephalopathy (PML), mycobacterium avium complex (MAC), cytomegalovirus (CMV), Pneumocystis pneumonia (PCP), or tuberculosis (TB)), which may necessitate further evaluation and treatment. In addition, autoimmune disease (including Graves' disease, Guillain-Barre syndrome, and polymyositis) may also develop; the time to onset is variable and may occur months after treatment initiation.
Antiretroviral therapy should be provided to all patients during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy (HAART) to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. Begin HAART as soon as pregnancy is recognized, or HIV is diagnosed. Ibalizumab-containing regimens are not recommended for routine use in pregnant patients; however, it may be appropriate to continue use of the drug in some heavily treatment-experienced pregnant patients without alternative options. If the decision is made with the patient to continue use of ibalizumab, frequent viral load monitoring (every 1 to 2 months) and patient counseling regarding a lack of safety data is recommended. No human data are available regarding ibalizumab use during pregnancy to evaluate for drug associated risk of major birth defects, miscarriages, or adverse maternal or fetal outcomes; however, data from cynomolgus monkeys has associated the use of ibalizumab during pregnancy with reversible immunosuppression (CD4 T cell and B cell lymphocytopenia) in the in utero-exposed infants. The clinical significance of this finding in humans is not known. If an infant is perinatally exposed to the drug, obtain an immune phenotype of the peripheral blood (including CD4 T cell and B cell counts) and consult an expert for guidance regarding monitoring and management based on the degree of immunosuppression observed. Monoclonal antibodies, such as ibalizumab, are increasingly transported across the placenta as pregnancy progresses with the largest amounts being transferred during the third trimester. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Patients who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than or equal to 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for patients on HAART less than 2 years and have CD4 counts less than 300 cells/mm3, patients with inconsistent adherence, or patients with detectable viral loads. For patients on HAART less than 2 years but have CD4 counts greater than or equal to 300 cells/mm3, monitor CD4 counts every 6 months. Monitor plasma HIV RNA at the initial visit (with review of prior levels), 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, and then at least every 3 months during pregnancy. Viral load should also be assessed at approximately 36 weeks gestation, or within 4 weeks of planned delivery, to inform decisions regarding mode of delivery and optimal treatment for newborns. Patients whose HIV RNA levels are above the threshold for resistance testing (usually greater than 500 copies/mL but may be possible for levels greater than 200 copies/mL in some laboratories) should undergo antiretroviral resistance testing (genotypic testing, and if indicated, phenotypic testing). Resistance testing should be conducted before starting therapy in treatment-naive patients who have not been previously tested, starting therapy in treatment-experienced patients (including those who have received pre-exposure prophylaxis), modifying therapy in patients who become pregnant while receiving treatment, or modifying therapy in patients who have suboptimal virologic response to treatment that was started during pregnancy. DO NOT delay initiation of antiretroviral therapy while waiting on the results of resistance testing; treatment regimens can be modified, if necessary, once the testing results are known. First trimester ultrasound is recommended to confirm gestational age and provide an accurate estimation of gestational age at delivery. A second trimester ultrasound can be used for both anatomical survey and determination of gestational age in those patients not seen until later in gestation. Perform standard glucose screening in patients receiving antiretroviral therapy at 24 to 28 weeks gestation, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for patients with high-risk factors for glucose intolerance. Liver function testing is recommended within 2 to 4 weeks after initiating or changing antiretroviral therapy, and approximately every 3 months thereafter during pregnancy (or as needed). All pregnant patients should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for development of resistance and perinatal transmission. It is strongly recommended that antiretroviral therapy, once initiated, not be discontinued. If a patient decides to discontinue therapy, a consultation with an HIV specialist is recommended. It is strongly recommended that health care providers report cases of antenatal antiretroviral drug exposure to the Antiretroviral Pregnancy Registry via telephone 800-258-4263; the Antiretroviral Pregnancy Registry is also accessible via the Internet. This registry does not include ibalizumab, but will likely include patients' concurrent antiretroviral medications. The FDA is requiring collection of prospective data on individuals exposed to ibalizumab during pregnancy to monitor maternal and infant outcomes.
HIV treatment guidelines recommend clinicians provide mothers with evidence-based, patient-centered counseling to support shared decision-making regarding infant feeding. Inform patients that use of replacement feeding (i.e., formula or banked pasteurized donor human milk) eliminates the risk of HIV transmission. Advise patients who receive a diagnosis of HIV infection while breast-feeding (acute HIV) to immediately discontinue breast-feeding and switch to replacement feeding in order to reduce the risk of postnatal HIV transmission to the infant. Replacement feeding is also recommended for use when mothers with HIV are not on antiretroviral therapy (ART) or do not have suppressed viral load during pregnancy, as well as at delivery. For patients on ART who have achieved and maintained viral suppression during pregnancy (at minimum throughout the third trimester) and postpartum, the transmission risk from breast-feeding is less than 1%, but not zero. Virologically suppressed mothers who choose to breast-feed should be supported in this decision. If breast-feeding is chosen, counsel the patient about the importance of adherence to therapy and recommend that the infant be exclusively breast-fed for up to 6 months of age, as exclusive breast-feeding has been associated with a lower rate of HIV transmission as compared to mixed feeding (i.e., breast milk and formula). Promptly identify and treat mastitis, thrush, and cracked or bleeding nipples, as these conditions may increase the risk of HIV transmission through breast-feeding. Breast-fed infants should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, healthcare workers may contact the Perinatal HIV Hotline (888-448-8765). There are no data available regarding the presence of ibalizumab in human milk, the effects on the breast-fed infant, 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 significant amounts.
Hypersensitivity reactions, including infusion-related reactions and anaphylactoid reactions, have been reported during postmarketing use of ibalizumab. Symptoms associated with these reactions have included angioedema, chest pain, chest tightness, cough, dyspnea, hot flush, nausea, vomiting, and wheezing. If signs and symptoms of a clinically significant hypersensitivity reaction occurs, immediately discontinue use of the drug and initiate appropriate treatment.
Counsel females of child-bearing potential about the reproductive risk associated with ibalizumab therapy. This reproductive risk was identified in a study involving cynomolgus monkeys, in which the use of ibalizumab during pregnancy caused reversible immunosuppression (i.e., CD4 T cell and B cell lymphocytopenia) in the in utero-exposed infants. In this study pregnant monkeys were administered 110 mg/kg of intravenous ibalizumab every week from gestation day 20 to 22 until birth on gestation day 160 (+/- 10 days). An evaluation of the infant monkeys found significant changes in immune cell concentrations on postnatal day 14 (78% mean decrease in CD4; 46% mean decrease in B cells; 2.3-fold mean increase in CD8) and postnatal day 28 (73% mean decrease in CD4; 2.2-fold mean increase in CD8). These lymphocyte changes correlated with infant ibalizumab serum concentrations and appeared to return to near normal between postnatal day 28 to 91 when the drug concentrations were nearly undetectable. No malformations, premature births, maternal toxicities (including no changes in maternal lymphocytes), or decreases in embryo-fetal survival were observed in this study; however, 1 infant monkey died on postnatal day 24 from a systemic viral infection which was acquired after birth. Although no human data are available, the risk of drug-induced immunosuppression in human infants is possible as monoclonal antibodies like ibalizumab are known to be transported across the placenta. If an infant is perinatally exposed to the drug, obtain an immune phenotype of the peripheral blood (including CD4 T cell and B cell counts) and consult an expert for guidance regarding monitoring and management based on the degree of immunosuppression observed. The safety of administering live or live-attenuated vaccines to an exposed infant is unknown.
Testing for human immunodeficiency virus (HIV) infection resistance is recommended in all antiretroviral treatment-naive patients at the time of HIV diagnosis, regardless of whether treatment will be initiated. Additionally, perform resistance testing prior to initiating or changing any HIV treatment regimen. Transmission of drug-resistant HIV strains has been both well documented and associated with suboptimal virologic response to initial antiretroviral therapy. The prevalence of transmitted drug resistance (TDR) in high-income countries ranges from 9% to 14% and varies by country. In most TDR surveys, non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance and nucleoside reverse transcriptase inhibitor (NRTI) resistance are the most common mutation class types detected, followed by protease inhibitor (PI) and integrase strand transfer inhibitor (INSTI) resistance mutations, respectively. Resistance testing at baseline can help optimize treatment and, thus, virologic response. In the absence of therapy, resistant viruses may decline over time to less than the detection limit of standard resistance tests, but may still increase the risk of treatment failure when therapy is eventually initiated. Thus, if therapy is deferred, resistance testing should still be performed during acute HIV infection with the genotypic resistance test result kept in the patient's medical record until it becomes clinically useful. Additionally, because of the possibility of acquisition of another drug-resistant virus before treatment initiation, repeat resistance testing at the time therapy is initiated would be prudent.
Perform hepatitis B virus (HBV) screening in any patient who presents with HIV infection to assure appropriate treatment. Patients with hepatitis B and HIV coinfection should be started on a fully suppressive antiretroviral (ARV) regimen with activity against both viruses (regardless of CD4 counts and HBV DNA concentrations). HIV treatment guidelines recommend these patients receive an ARV regimen that contains a dual NRTI backbone of tenofovir alafenamide or tenofovir disoproxil fumarate with either emtricitabine or lamivudine. If tenofovir cannot be used, entecavir should be given in combination with a fully suppressive ARV regimen (note: entecavir should not be considered part of the ARV regimen). Avoid using single-drug therapy to treat HBV (i.e., lamivudine, emtricitabine, tenofovir, or entecavir as the only active agent) as this may result in HIV resistant strains. Further, HBV treatment regimens that include adefovir or telbivudine should also be avoided, as these regimens are associated with a higher incidence of toxicities and increased rates of HBV treatment failure. Most patients with coinfection should continue treatment indefinitely with the goal of maximal HIV suppression and prevention of HBV relapse. If treatment must be discontinued, monitor transaminase concentrations every 6 weeks for the first 3 months, and every 3 to 6 months thereafter. For patients who refuse a fully suppressive ARV regimen, but still require treatment for HBV, consider 48 weeks of peginterferon alfa; do not administer HIV-active medications in the absence of a fully suppressive ARV regimen. Instruct patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate.
HIV treatment guidelines recommend all patients presenting with HIV infection undergo routine screening for hepatitis C virus (HCV). For HCV seronegative individuals who are at continued high risk of acquiring hepatitis C, specifically men who have sex with men (MSM) or persons who inject drugs, additional HCV screening is recommended annually or as indicated by clinical presentation (e.g., unexplained ALT elevation), risk activities, or exposure. Similarly, the AASLD/IDSA HCV guidelines and the CDC preexposure prophylaxis (PrEP) guidelines recommend HCV serologic testing at baseline and every 12 months for MSM, transgender women, and persons who inject drugs. Use an FDA-approved immunoassay licensed for detection of HCV antibodies (anti-HCV); in settings where acute HCV infection is suspected or in persons with known prior infection that cleared spontaneously or after treatment, use of nucleic acid testing for HCV RNA is recommended. If hepatitis C and HIV coinfection is identified, consider treating both viral infections concurrently. It is recommended to use a fully suppressive antiretroviral therapy and an HCV regimen in all patients with coinfection regardless of CD4 count, as lower CD4 counts do not appear to compromise the efficacy of HCV treatment. In most patients, a simplified pangenotypic HCV regimen (i.e., glecaprevir; pibrentasvir or sofosbuvir; velpatasvir) may be an appropriate choice; however, these regimens are NOT recommended for use in persons with HCV and HIV coinfection who: are treatment-experienced with HCV relapse (reinfection after successful therapy is not an exclusion); have decompensated cirrhosis; on a tenofovir disoproxil fumarate containing regimen with eGFR less than 60 mL/minute; on efavirenz, etravirine, nevirapine, or boosted protease inhibitor; have untreated chronic hepatitis B; are pregnant. Patients with HCV and HIV coinfection who meet these exclusion criteria should be treated for HCV following standard approaches as described in the AASLD/IDSA HCV guidelines. Treatment of HCV infection in children younger than 3 years is not usually recommended; however, treatment should be considered for all children 3 years and older with HCV and HIV coinfection who have no contraindications to treatment. Instruct patients with coinfection to avoid consuming alcohol, limit ingestion of potentially hepatotoxic medications, avoid iron supplementation in the absence of documented iron deficiency, and receive vaccinations against hepatitis A and hepatitis B as appropriate.
Initiation of therapy for HIV infection:
-For adults, initiation of treatment immediately (or as soon as possible) after HIV diagnosis is recommended in all patients to reduce the risk of disease progression and to prevent the transmission of HIV, including perinatal transmission and transmission to sexual partners. Starting antiretroviral therapy early is particularly important for patients with AIDS-defining conditions, those with acute or recent HIV infection, and individuals who are pregnant; delaying therapy in these subpopulations has been associated with high risks of morbidity, mortality, and HIV transmission.
-Prior to initiating treatment, obtain baseline plasma HIV RNA (viral load) and CD4 count; results do not need to be available before starting therapy.
-Antiretroviral drug-resistance testing:
--Genotypic drug-resistance testing is recommended prior to initiation of therapy and prior to changing therapy for treatment failure.
--Standard genotypic drug-resistance testing in treatment-naive people should focus on testing for mutations in reverse transcriptase (RT) and protease (PR) genes.
-Testing for mutations in the integrase gene should also be performed if integrase strand transfer inhibitor (INSTI) resistance is a concern (e.g., people who acquire HIV after pre-exposure prophylaxis with long-acting cabotegravir).
-Phenotypic resistance testing may be used in conjunction with the genotypic test for patients with known or suspected complex drug-resistance mutation patterns.
-HIV-1 proviral DNA resistance testing is available for use in patients with HIV RNA concentrations below the limits of detection or with low-level viremia (i.e., less than 1,000 copies/mL), where genotypic testing is unlikely to be successful; however, the clinical utility of this assay has not been fully determined.
-It is not necessary to delay treatment until resistance test results are available; however, subsequent modifications to the treatment regimen should be made, if needed, once the test results are available.
-Pediatric guidelines are also available.
Place in therapy for HIV infection:
-Ibalizumab is used as part of combination therapy in heavily treatment-experienced adults with multidrug-resistant HIV-1 infections failing their current antiretroviral regimen. The drug has also demonstrated potent in vitro activity against HIV-2 and may be considered for treatment of multidrug-resistant HIV-2 infections.
-Data are limited regarding the use of ibalizumab during pregnancy; therefore, routine use of ibalizumab in pregnant patients cannot be recommended. However, it may be appropriate to continue use of the drug in some heavily treatment-experienced pregnant patients without alternative options.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: human immunodeficiency virus (HIV)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of human immunodeficiency virus (HIV) infection:
Intravenous dosage:
Adults: 2,000 mg IV once, then 800 mg IV every 2 weeks as part of combination therapy in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen.
Maximum Dosage Limits:
-Adults
2,000 mg IV once, then 800 mg IV every 2 weeks.
-Geriatric
2,000 mg IV once, then 800 mg IV every 2 weeks.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Ibalizumab products.
Ibalizumab, an intravenous recombinant humanized monoclonal antibody, works by blocking HIV-1 from infecting CD4 T cells by binding to domain 2 of CD4 and interfering with post-attachment steps required for the entry of HIV-1 virus particles into host cells and preventing the viral transmission that occurs vial cell-cell fusion. The binding specificity of ibalizumab to domain 2 of CD4 allows ibalizumab to block viral entry into host cells without causing immunosuppression.
Decreased susceptibility to ibalizumab, as defined by a decrease in maximum percent inhibition, has been noted in some subjects experiencing virologic failure and may be associated with genotypic changes in the HIV-1 envelope coding sequence that results in the loss of potential N-linked glycosylation sites (PNGS) in the V5 loop of gp120. The clinical significance of decreased susceptibility to ibalizumab has not been established.
Phenotypic and genotypic test results revealed no evidence of cross-resistance between ibalizumab and any of the approved classes of antiretroviral drugs. Ibalizumab is active against HIV-1 resistant to all approved antiretroviral drugs and exhibits antiretroviral activity against R5-tropic, X4-tropic, and dual-tropic HIV-1.
Ibalizumab has demonstrated potent in vitro activity against HIV-2 isolates.
Ibalizumab is administered intravenously (IV). It displays nonlinear pharmacokinetics when given as a single agent. Following single-dose administration of ibalizumab as 0.5 to 1.5-hour infusions, the AUC increased in a greater than dose-proportional manner, clearance decreased from 9.5 to 0.36 mL/kg/hour, and elimination half-life increased from 2.7 to 6.4 hours as the dose increased from 0.3 to 25 mg/kg. The Vd of ibalizumab was approximately that of serum volume at 4.8 L. Following the recommended dose regimen (single IV loading dose of 2,000 mg, followed by 800 mg IV every 2 weeks), ibalizumab concentrations reached steady state levels after the first 800 mg maintenance dose with mean concentrations over 30 mcg/mL throughout the dosing interval. It is predicted that administration of the initial 2,000 mg loading dose as an IV push over 90 seconds will have similar Cmax and AUC values as an IV infusion administered over 30 minutes. Among patients living with HIV, pharmacokinetic data show that ibalizumab Ctrough and AUC values for IV push and IV infusion maintenance doses are similar. However, the Cmax values are 25% higher for the maintenance IV push compared to the infusion; this increase in Cmax is not considered clinically relevant.
Affected cytochrome P450 isoenzymes: none
No drug interaction studies have been conducted with ibalizumab; however, based on its mechanism of action and target-mediated drug disposition, drug-drug interactions are not expected.
-Special Populations
Hepatic Impairment
The pharmacokinetics of ibalizumab have not been evaluated in patients with hepatic impairment.
Renal Impairment
The pharmacokinetics of ibalizumab have not been evaluated in patients with renal impairment; however, renal impairment is not expected to impact the pharmacokinetics of ibalizumab.
Pediatrics
The pharmacokinetics of ibalizumab have not been evaluated in pediatric patients.
Geriatric
The pharmacokinetics of ibalizumab have not been evaluated in geriatric patients.
Obesity
Results from a pharmacokinetic analysis suggested that ibalizumab concentrations decrease as body weight increases; however, the effect is unlikely to affect virologic outcomes and does not warrant a dose adjustment.