Xembify

Aug 1, 2022

Generic name:  immune globulin subcutaneous, human-klhw
Dosage form: subcutaneous injection
Drug class:  Immune globulins

WARNING: THROMBOSIS

  • Thrombosis may occur with immune globulin products, including Xembify. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors. [see  Warnings and Precautions (5.2) ,  Patient Counseling Information (17) ]
  • For patients at risk of thrombosis, administer Xembify at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. [see  Warnings and Precautions (5.2) ]

Indications and Usage for Xembify

Xembify® (immune globulin subcutaneous, human – klhw) is a 20% immune globulin solution for subcutaneous injection indicated for treatment of primary humoral immunodeficiency (PI) in patients 2 years of age and older. This includes, but is not limited to, congenital agammaglobulinemia, common variable immunodeficiency, X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.[ 1-4 ]

Xembify Dosage and Administration

For subcutaneous infusion only.

Before switching to Xembify, obtain the patient’s serum IgG trough level to guide subsequent dose adjustments.

Dose

Individualize the dose based on the patient’s pharmacokinetic and clinical response.

Measure the patient’s serum IgG trough level as early as 5 weeks after initiating Xembify treatment to determine if a dose adjustment is needed.

Monitor the patient’s IgG trough level every 2 to 3 months to determine subsequent dose adjustments and dosing intervals as needed ( Table 1 ).

Doses divided over the course of a week or once weekly achieve similar exposure when administered regularly at steady-state.

For frequent dosing (2-7 times per week), divide the calculated weekly dose by the desired number of times per week.

For dose adjustments, calculate the difference (in mg/dL) of the patient’s serum IgG trough level from the target IgG trough level, then find this difference in Table 1 (below). Locate the corresponding amount (in mL) by which to increase or decrease the weekly dose based on the patient’s body weight. For example, if a patient with a body weight of 70 kg has an actual IgG trough level of 900 mg/dL and the target level is 1,000 mg/dL, this results in a difference of 100 mg/dL. Therefore, increase the weekly dose of subcutaneous dose by 5 mL.

The patient’s clinical response should be the primary consideration in dose adjustment. If a patient on Xembify does not maintain an adequate clinical response or a serum IgG trough level equivalent to that of a previous treatment, adjust the dose accordingly.

Difference From Target
IgG Trough
Level (mg/dL)
Body Weight (kg)
10152030405060708090100110120
Dose Adjustment (mL per Week) *
500111222333445
1001122345567889
15012235678910111314
2002235689111214151718
25023468911131517192123
300235791114161820232527
3503458111316192124272932
4003569121518212427303336
45035710141720242731343841
50046811151923273034384245
* Dose adjustment in mL is based on the slope of the serum IgG trough level response to subcutaneous administration of Xembify dose increments (about 6.6 mg/dL per increment of 1 mg/kg per week).

Switching to Xembify from IVIG

Begin treatment with Xembify one week after the patient’s last IVIG infusion. Calculate the initial weekly dose of Xembify. Divide the previous monthly (or every 3 weeks) IVIG dose in grams by the number of weeks between IVIG infusions, then multiply this dose by the dose adjustment factor of 1.37.

To convert the Xembify dose (in grams) to milliliters (mL), multiply the calculated Initial SC dose (in grams) by 5.

Provided the total weekly dose is maintained, any dosing interval from daily up to weekly will achieve similar systemic IgG exposure when administered regularly at steady-state.

Switching to Xembify from subcutaneous immune globulin (IGSC)

Administer the same weekly dose of Xembify (in grams) as the weekly dose of prior IGSC treatment (in grams).

Preparation and Handling

Xembify is a clear to slightly opalescent, and colorless or pale yellow solution.

Visually inspect Xembify for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not use if the solution is cloudy or turbid.

Do not shake.

Do not dilute.

The Xembify vial is for single use only.

Do not store any vial that has been entered by a needle during preparation for infusion, punctured, partially used, or opened.

Administer within 8 hours after beginning infusion preparation (i.e., once Xembify is transferred from the vial into a syringe).

Administer Xembify separately from other drugs or medications that the patient may be receiving.

Do not mix Xembify with other medications including immune globulins from other manufacturers.

Do not use after expiration date.

Discard unused portion.

Administration

For subcutaneous infusion only.

Prior to use, allow the solution to reach ambient room temperature.
Do not shake.
Follow the steps below and use aseptic technique to administer Xembify.

1. Inspect the vials: inspect for clarity, color, and expiration date (s).

2. Prepare for infusion:

Gather supplies: Xembify vial(s), ancillary supplies, sharps container, patient’s
treatment diary/logbook, and the infusion pump.

Prepare a clean work area.

Wash hands.

3. Remove the protective cap from the vial to expose the central portion of the stopper.

If the packaging shows any sign of tampering, do not use the product and notify
Grifols Therapeutics LLC immediately [1-800-520-2807].

4. Wipe the stopper with alcohol and allow to dry.

5.Using a sterile syringe and needle, prepare to withdraw Xembify by first injecting air into the vial that is equivalent to the amount of Xembify to be withdrawn. Then withdraw the desired volume of Xembify. If multiple vials are required to achieve the desired dose, repeat this step. (Figure 1)

6.Use Xembify as soon as practicable, within 2 hours to avoid the potential formation of particles caused by siliconized syringes.
7.Follow the manufacturer’s instructions for preparing the pump and administration tubing. Be sure to prime the administration tubing to ensure that no air is left in the tubing or needle by filling the tubing/needle with Xembify.
8.Select the number and location of injection sites. Rotate sites for each administration. (Figure 2)

Infuse Xembify in the abdomen, thigh, upper arm, sides, back and/or lateral hip.

Avoid bony areas, scars, areas of inflammation, superficial infection or blood vessels.
9.Cleanse the injection site(s) with antiseptic solution using a circular motion working from the center of the site and moving to the outside. Sites should be clean, dry, and at least 2 inches (5cm) apart. (Figure 3)
10.Grasp the skin between 2 fingers (pinch at least one inch (2.5cm) of skin) and insert the needle at a 90-degree angle into the subcutaneous tissue. (Figure 4)
11.After inserting each needle, make sure that a blood vessel has not been accidentally entered. Attach a sterile syringe to the end of the primed administration tubing, pull back on the plunger, and if you see blood, remove and discard the needle and administration tubing. (Figure 5)

12. Repeat priming and needle insertion steps using a new needle, administration tubing
and a new infusion site. Secure the needle in place by applying sterile gauze or
transparent dressing over the site.

13. Infuse Xembify at a maximum rate of 25 mL per hour per infusion site using up to
6 infusion sites (most patients used 4 infusion sites). Ensure that the infusion sites are
at least 2 inches (5 cm) apart for patients of all ages. The number of infusion sites is
at healthcare provider discretion. Children will require less total volume for a specific
Xembify dose (mg/kg body weight) than adults. The healthcare provider may
choose a smaller volume/site for children and/or fewer infusion sites to achieve the
target total dose, depending on the needs of the child. The total dose volume of
Xembify is divided by the desired volume (mL/site) to obtain number of infusion
sites to be used.

Volume to Be
Infused SC
RateNumber of Sites
(most frequent is 4)
Site Distance
Apart
25 mL per site≤ 25 mL/hr/infusion site≤ 6≥ 2 inches (5 cm)

Record information about the infusion (e.g., lot number, expiration date, dose, date,
time, infusion site location(s), side effects) in a patient treatment record or infusion
log.

14. Discard the needle(s) and infusion line(s) in an appropriate container. Follow the
manufacturer’s instructions for storage of the infusion pump.

15. Discard partially used vial(s).

Dosage Forms and Strengths

Xembify is a protein solution containing 20% IgG (200 mg/mL; 0.2 g/mL) for subcutaneous infusion.

Contraindications

Xembify is contraindicated in:

Patients who have had an anaphylactic or severe systemic reaction to the administration of human immune globulin.

IgA deficient patients with antibodies against IgA and history of hypersensitivity to human immune globulin treatment.

Warnings and Precautions

Hypersensitivity

Severe hypersensitivity reactions may occur with human immune globulin products, including Xembify. If a hypersensitivity reaction occurs, discontinue the Xembify infusion immediately and institute appropriate treatment.

Xembify contains IgA. Patients with known anti-IgA antibodies have a greater risk of developing potentially severe hypersensitivity and/or anaphylactic reactions. Xembify is contraindicated in IgA deficient patients with antibodies against IgA and history of hypersensitivity to human immune globulin treatment. [see  Contraindications (4) ]

Thrombosis

Thrombosis may occur following treatment with immune globulin products, including Xembify.[ 5-7 ] Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors.

Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies. For patients at risk of thrombosis, administer Xembify at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. [see  Boxed Warning, Dosage and Administration (2.3) ,  Patient Counseling Information (17) ]

Aseptic Meningitis Syndrome (AMS)

AMS has been reported with the use of human immune globulin administered intravenously and subcutaneously. It usually begins within several hours to 2 days following immune globulin treatment. AMS may occur more frequently in females than in males.

AMS is characterized by the following signs and symptoms: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea and vomiting. Cerebrospinal fluid (CSF) studies frequently show pleocytosis up to several thousand cells per cubic millimeter, predominantly from the granulocytic series, and elevated protein levels up to several hundred mg/dL, but negative culture results. To rule out other causes of meningitis, conduct a thorough neurological examination on patients exhibiting such symptoms and signs, including CSF studies. AMS may occur more frequently in association with high doses (>2 g/kg) and/or rapid infusion of immune globulin products. Discontinuation of immune globulin treatment has resulted in remission of AMS within several days without sequelae.

Renal Dysfunction/Failure

Acute renal dysfunction/failure, acute tubular necrosis, proximal tubular nephropathy, osmotic nephrosis and death may occur upon use of human immune globulin products, especially those containing sucrose.[ 8,9 ] Xembify does not contain sucrose. Ensure that patients are not volume depleted prior to administration of Xembify.

In patients at risk of developing renal dysfunction, including patients with any degree of preexisting renal insufficiency or predisposition to acute renal failure (such as diabetes mellitus, age greater than 65 years, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs), monitor renal function and consider lower, more frequent dosing. [see  Dosage and Administration (2.3) ]

Periodic monitoring of renal function and urine output is particularly important in patients judged to have a potential increased risk for developing acute renal failure. Assess renal function, including measurement of blood urea nitrogen (BUN)/serum creatinine, prior to the initial infusion of Xembify and again at appropriate intervals thereafter. If renal function deteriorates, consider discontinuation of Xembify. [see  Patient Counseling Information (17) ]

Hemolysis

IgG products, including Xembify can contain blood group antibodies that may act as hemolysins and induce in vivo coating of red blood cells (RBCs) with immunoglobulin, causing a positive direct antiglobulin (Coombs’) test result and hemolysis.[ 10-13 ] Delayed hemolytic anemia can develop subsequent to human immune globulin therapy due to enhanced RBC sequestration, and acute hemolysis consistent with intravascular hemolysis has been reported. [see  Adverse Reactions (6) ]

Monitor Xembify recipients for clinical signs and symptoms of hemolysis, particularly patients with risk factors such as non-O blood group, or patients receiving high IgG doses (≥ 2 grams/kg).[ 14 ] Underlying inflammatory state in an individual patient may increase the risk of hemolysis, but its role is uncertain.[ 15 ]

If signs and/or symptoms of hemolysis are present after Xembify infusion, perform appropriate confirmatory laboratory testing.

Transfusion-related Acute Lung Injury (TRALI)

Noncardiogenic pulmonary edema may occur in patients following treatment with human immune globulin products.[ 16 ] TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Symptoms typically occur within 1 to 6 hours after treatment.

Monitor patients for pulmonary adverse reactions. If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil and anti-HLA antibodies in both the product and patient serum. TRALI may be managed using oxygen therapy with adequate ventilatory support.

Transmissible Infectious Agents

Because Xembify is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. This also applies to unknown or emerging viruses and other pathogens. No cases of transmission of viral diseases or CJD have been associated with the use of Xembify. ALL infections suspected by a physician to have possibly been transmitted by Xembify should be reported by the physician or other healthcare provider to Grifols Therapeutics LLC [1-800-520-2807].

Interference with Laboratory Tests

After infusion with Xembify, the transitory rise of various passively transferred antibodies in the patient’s blood may yield false-positive serological testing results, with the potential for misleading interpretation. Passive transmission of antibodies to erythrocyte antigens (e.g., A, B, and D) may cause a positive direct or indirect antiglobulin (Coombs’) test.

Adverse Reactions

The most common adverse reactions in ≥ 5% of subjects in the clinical trial were local adverse reactions including infusion site erythema (redness), infusion site pain, infusion site swelling (puffiness), infusion site bruising, infusion site nodule, infusion site pruritus (itching), infusion site induration (firmness), infusion site scab, infusion site edema, and systemic reactions including cough and diarrhea.

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of one drug cannot be directly compared to rates in other clinical trials of another drug and may not reflect the rates observed in clinical practice.

Clinical safety data are based on an open-label, single-arm prospective multi-center study of 49 subjects with primary immunodeficiency (PI) who received subcutaneous Xembify for at least 6 months.

A total of 49 subjects received 1053 Xembify infusions, including 14 subjects between 2 to 16 years of age during the clinical trial. The average number of infusions per subject was 21.5 infusions, median 24 infusions (range 1-26 infusions). There were a total of 390 local infusion site reactions which occurred at a rate per infusion of 0.370 (about 1 in 2.7 infusions). Of these, the most common was infusion site erythema which had a median duration of 24.9 hours. Infusion site swelling, and infusion site pain had median durations of 24.5 and 22.8 hours, respectively. Local infusion site reactions of all kinds by site of infusion (where site of infusion was recorded) occurred in 50.0% and 52.6% of patients during infusions in the abdomen versus thigh, respectively, and across 773 abdominal infusions and 279 thigh infusions rates were 0.184 and 0.735 per infusion, respectively; this corresponds to 1 in 5.4 infusions (for abdomen) and 1 in 1.4 infusions (for thigh). No local infusion site reactions were severe or serious.

The adverse reactions occurring in ≥ 5% of subjects on Xembify in the clinical trial for the duration of the subcutaneous (SC) phase are depicted in the table below which includes all treatment-emergent adverse reactions except infections.

Adverse Reaction * By Subject
n (%) †
(N=49 subjects)
By Infusion
n (rate) ‡
(N=1053 infusions)
Infusion site erythema19 (39%)123 (0.117)
Infusion site pain9 (18%)32 (0.030)
Infusion site swelling8 (16%)124 (0.118)
Infusion site bruising8 (16%)26 (0.025)
Infusion site nodule8 (16%)13 (0.012)
Infusion site pruritus5 (10%)28 (0.027)
Infusion site induration4 (8%)6 (0.006)
Infusion site scab3 (6%)6 (0.006)
Infusion site edema3 (6%)5 (0.005)
Cough3 (6%)4 (0.004)
Diarrhea3 (6%)3 (0.003)
* Including all adverse reactions that occurred after the first dose of Xembify regardless of causality, excluding infections. † Number and percentage of subjects with the adverse reaction. ‡ Rate per infusion is calculated as the total number of adverse reactions divided by the total number of infusions.

Four subjects discontinued Xembify due to adverse reactions which were infusion site nodules, infusion site discomfort, skin papules/plaques, and arthralgia/myalgia.

Postmarketing Experience

Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure.

The following adverse reactions have been identified and reported during the postmarketing use of immune globulin products administered subcutaneously:

Cardiac disorders: Tachycardia

Nervous system disorders: Tremor and paresthesia

Respiratory, thoracic and mediastinal disorders: Dyspnea and laryngospasm

Drug Interactions

Serological Testing

Various passively transferred antibodies in immunoglobulin preparations, including Xembify, can confound the results of serological testing.

Live Attenuated Virus Vaccines

Passive transfer of antibodies may transiently interfere with the immune response to live virus vaccines such as measles, mumps, rubella and varicella. Inform the immunizing healthcare provider of recent therapy with Xembify so that appropriate measures may be taken.

USE IN SPECIFIC POPULATIONS

Pregnancy

Risk Summary

No human data are available to indicate the presence or absence of drug associated risk. Animal reproduction studies have not been conducted with Xembify. It is not known whether Xembify can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Immune globulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Lactation

Risk Summary

No human data are available to indicate the presence or absence of drug associated risk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Xembify and any potential adverse effects on the breastfed infant from Xembify or from the underlying maternal condition.

Pediatric Use

Xembify was evaluated in 14 pediatric subjects with PI (2-16 years of age) in a multi-center clinical trial. The safety and efficacy profiles were similar to adult subjects. No pediatric-specific dose requirements were necessary to achieve the desired serum IgG levels.

Geriatric Use

Clinical studies of Xembify did not include sufficient numbers of subjects over age 65 years to determine whether they respond differently from younger subjects. Three study subjects enrolled in the clinical trial were 65 years and older. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Xembify Description

Xembify, immune globulin subcutaneous, human-klhw, is a 20% ready-to-use sterile, non-pyrogenic solution of human immune globulin protein for subcutaneous administration. The purity is ≥ 98% IgG with a sub-class distribution similar to that found in normal serum.

Xembify consists of 18% to 22% protein in 0.16 M to 0.26 M glycine and 10 to 40 mcg/mL polysorbate 80 at a pH of 4.1 to 4.8. The solution is clear to slightly opalescent, and colorless or pale yellow. The osmolality range is 280 to 404 mOsmol/kg. Xembify contains no preservative and is not made with natural rubber latex.

Xembify is made from large pools of human plasma by a combination of cold ethanol fractionation, caprylate precipitation and filtration, and anion-exchange chromatography. Isotonicity is achieved by the addition of glycine. Xembify is incubated in the final container (at the low pH of 4.1 to 4.8).

The capacity of the manufacturing process to remove and/or inactivate enveloped and non-enveloped viruses has been validated by laboratory spiking studies on a scaled down process model, using the following enveloped and non-enveloped viruses: human immunodeficiency virus, type I (HIV-1) as the relevant virus for HIV-1 and HIV-2; bovine viral diarrhea virus (BVDV) as a model for hepatitis C virus; pseudorabies virus (PRV) as a model for large enveloped DNA viruses (e.g. herpes viruses); West Nile Virus (WNV) as a relevant virus; Reovirus type 3 (Reo) as a model for non-enveloped viruses and for its resistance to physical and chemical inactivation; hepatitis A virus (HAV) as relevant non-enveloped virus, and porcine parvovirus (PPV) as a model for human parvovirus B19.

Overall virus clearance capacity was calculated only from steps that were mechanistically independent from each other and truly additive. In addition, each step was verified to provide robust virus reduction across the production range for key parameters.

Process StepEnveloped VirusNon-Enveloped Virus
HIV-1BVDVPRVWNVReo3HAVPPV
Caprylate Precipitation/Depth FiltrationC/I * .2.7C/I * C/I * ≥3.5≥3.64.0
Caprylate Incubation † ≥4.5≥4.5≥4.6≥5.1NA ‡ NA ‡ NA ‡
Column Chromatography≥3.04.0≥3.3ND § ≥4.0≥1.44.2
Nanofiltration≥3.7≥4.1ND § ND § ≥1.8ND § 0.5
Low pH Final Container Incubation≥5.34.9≥5.1≥5.3NA ‡ NA ‡ NA ‡
Overall Clearance Capacity≥16.5≥20.2≥13.0≥10.4≥9.3≥5.08.2
* C/I: Interference by caprylate precluded determination of virus clearance capacity for this step † DHBV and SINV were also evaluated for the caprylate incubation step. The log10 clearance capacities were ≥3.6 and ≥6.0, respectively. ‡ NA = Not applicable: This step is not applicable to non-enveloped viruses. § Due to interfering effects of the process intermediate matrix the virus clearance capacity could not be determined.

Additionally, the manufacturing process was investigated for its capacity to decrease the infectivity of an experimental agent of transmissible spongiform encephalopathy (TSE), considered as a model for the variant Creutzfeldt-Jakob disease (vCJD), and Creutzfeldt-Jakob disease (CJD) agents.

Several of the individual production steps of the manufacturing process have been shown to decrease TSE infectivity of an experimental model agent. TSE reduction steps include depth filtrations (a total of ≥ 6.6 log10). These studies provide reasonable assurance that low levels of vCJD/CJD agent infectivity, if present in the starting material, would be removed.

Xembify – Clinical Pharmacology

Mechanism of Action

Xembify supplies a broad spectrum of opsonizing and neutralizing immunoglobulin G (IgG) antibodies against bacterial, viral, parasitic, and mycoplasmal agents and their toxins. Xembify also contains a spectrum of antibodies capable of interacting with and altering the activity of cells of the immune system. The role of these antibodies and the mechanism of action of Xembify are not fully understood.

Pharmacodynamics

Human normal immunoglobulin contains mainly (IgG) with a broad spectrum of antibodies against infectious agents. Human normal immunoglobulin contains the IgG antibodies present in the normal population. Xembify has a distribution of IgG subclasses closely proportional to that in native human plasma. Adequate doses of Xembify may restore abnormally low IgG levels to the normal range.

Pharmacokinetics

Pharmacokinetic (PK) parameters of subcutaneously administered Xembify were evaluated in subjects with primary immunodeficiency (PI) during a clinical trial. [see  Clinical Studies (14) ] Subjects were treated intravenously with a comparator product [GAMUNEX®-C, immune globulin injection (human), 10% caprylate/chromatography purified] during a 3-4 months run-in period prior to IV PK profiling in 50 subjects, and then 49 subjects switched to weekly subcutaneous infusions of Xembify for 24 weeks at 137% of the intravenous dose with PK profiling at SC Week #13-14. A comparison of the area under the curve (AUC) for subcutaneous versus intravenous infusion was performed.

At this dose adjustment, the geometric least-squares means ratio of the AUC for subcutaneous Xembify versus IV administration of GAMUNEX-C was 104% (90% CI: 100%-107%). The peak IgG level occurred at a mean of 76 hours after subcutaneous Xembify administration. The average mean IgG trough level at steady state was higher with Xembify (1245 mg/dL) compared with IV GAMUNEX-C (957 mg/dL) (average mean trough ratio SC/IV of 1.3). PK parameters of Xembify are summarized in  Table 4 . PK parameters did not significantly differ between age groups ( Table 5 ).

PhaseStatisticsAUC(0-7 days)
(h*mg/mL) *
Cmax (mg/mL)tmax (hour)
IVn494949
Mean±SD2122±41822±45.814
CV%2020
SCn394141
Mean±SD2183±48114±376±36
CV%222247
Min, Max1027, 36756, 230, 168 †
* AUC(0-7 days) in the IV Phase is calculated as AUC(0-21 days)/3 for subjects on an every-3-week IV dosing schedule (n=6), and as AUC(0-28 days)/4 for subjects on an every-4-week IV dosing schedule (n=43). † The apparent variability in tmax in the SC Phase can be attributed to the low fluctuation in IgG concentrations and is unlikely to be of any clinical relevance.

Age Group
(years)
Statistics
AUC(0-7 days)
(h*mg/mL)
Cmax (mg/mL)Mean Trough
(mg/mL)
tmax (hour)
2 -5 (n)1111
Mean±SD1839±NC * 11±NC * 11± NC * 72±NC *
>5 -12 (n)5565
Mean±SD2156±27614±212±271±26
CV%131315.337.16
Min, Max1878, 245612, 1610, 1528.2, 100.8
>12 -16 (n)4555
Mean±SD2400±40615±314±273±50
CV%171815.268.44
Min, Max2056, 298713, 2011, 1723.7, 143.1
>16 (n)29303230
Mean±SD2170±52414±312±378±36
CV%242423.946.66
Min, Max1027, 36756, 237, 200.00, 167.7
* NC = Not calculated

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No nonclinical studies were conducted to evaluate the carcinogenic or mutagenic effects of Xembify or its effects on fertility.

Animal Toxicology and/or Pharmacology

Single and repeated dose toxicology studies were conducted in male New Zealand White rabbits. In a single-dose toxicity study, no adverse effects were observed with subcutaneous dose levels of 500, 1000 and 1500 mg/kg. In a repeated-dose toxicity study, the systemic safety and toxicity profiles of Xembify and comparator GAMUNEX-C were similar following 5 consecutive daily subcutaneous doses at levels of 500, 1000 and 1500 mg/kg/day. Transient local injection site swelling was observed in Xembify but not in the GAMUNEX-C groups.

In improper delivery route studies, Xembify administered as a single intravenous, intra-arterial or perivascular dose of 100 mg/kg caused injection site irritation in New Zealand White rabbits. The findings were of higher incidence following perivascular administration of either Xembify or GAMUNEX-C, and were within the norms of this route of administration in this species.

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