Thrombosis may occur with immune globulin products, including HYQVIA. Risk factors may include advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors. [see Warnings and Precautions (5.2) ] For patients at ri...
HYQVIA is indicated for the treatment of Primary Immunodeficiency (PI) in adults and pediatric patients two years of age and older. This includes, but is not limited to, common variable immunodeficiency (CVID), X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies. HYQVIA is indicated for the treatment of chronic inflammatory demyelinating poly...
For subcutaneous use only The recommended Recombinant Human Hyaluronidase (rHuPH20) dose is 80 U/g Immune Globulin (IgG), which corresponds to 0.5 mL rHuPH20 solution per 10 mL Immune Globulin Infusion (Human), 10% solution for both indications. The recommended Immune Globulin Infusion (Human), 10% dose is given below. Primary Immunodeficiency (PI) Initiation of Treatment with HYQVIA For patients previously on ano...
How Supplied HYQVIA is supplied in a dual vial unit of two single dose vials containing the labeled amount of functionally active Immune Globulin Infusion (Human), 10% and rHuPH20. The packaging of this product is not made with natural rubber latex. The following presentations of HYQVIA are available: Immune Globulin Infusion (Human), 10% rHuPH20 NDC Number Volume Grams Protein Volume Units 0944-2510-02 25 mL 2.5 ...
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www.immunedisease.comHYQVIA is indicated for the treatment of Primary Immunodeficiency (PI) in adults and pediatric patients two years of age and older. This includes, but is not limited to, common variable immunodeficiency (CVID), X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.
HYQVIA is indicated for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment in adults.
For subcutaneous use only
The recommended Recombinant Human Hyaluronidase (rHuPH20) dose is 80 U/g Immune Globulin (IgG), which corresponds to 0.5 mL rHuPH20 solution per 10 mL Immune Globulin Infusion (Human), 10% solution for both indications.
The recommended Immune Globulin Infusion (Human), 10% dose is given below.
Primary Immunodeficiency (PI)
Initiation of Treatment with HYQVIA
| Week | Infusion Number | Dose Interval | Example for 30 grams per 4 weeks |
|---|---|---|---|
| 1 | 1st infusion | 1-week-dose | 7.5 grams |
| 2 | 2nd infusion | 2-week-dose | 15 grams |
| 3 | No infusion | Not Applicable (NA) | NA |
| 4 | 3rd infusion | 3-week-dose | 22.5 grams |
| 5 | No infusion | NA | NA |
| 6 | No infusion | NA | NA |
| 7 | 4th infusion (if required) | 4-week-dose | 30 grams |
For patients switching from Immune Globulin Intravenous (Human) [IGIV] treatment:
For patients at risk for measles exposure:
For patients naïve to Immune Globulin Subcutaneous (Human) [IGSC] treatment or switching from IGSC treatment:
Individualization of Dose
For dose adjustment:
| Body Weight | 100 mg/dL | 200 mg/dL | 300 mg/dL | 400 mg/dL |
|---|---|---|---|---|
| 10 kg | 3 mL | 6 mL | 9 mL | 12 mL |
| 20 kg | 6 mL | 12 mL | 18 mL | 24 mL |
| 30 kg | 9 mL | 18 mL | 27 mL | 36 mL |
| 40 kg | 12 mL | 24 mL | 36 mL | 48 mL |
| 50 kg | 15 mL | 30 mL | 45 mL | 61 mL |
| 60 kg | 18 mL | 36 mL | 55 mL | 73 mL |
| 70 kg | 21 mL | 42 mL | 64 mL | 85 mL |
| 80 kg | 24 mL | 48 mL | 73 mL | 97 mL |
| 90 kg | 27 mL | 55 mL | 82 mL | 109 mL |
| 100 kg | 30 mL | 61 mL | 91 mL | 121 mL |
| 110 kg | 33 mL | 67 mL | 100 mL | 133 mL |
| 120 kg | 36 mL | 73 mL | 109 mL | 145 mL |
| 130 kg | 39 mL | 79 mL | 118 mL | 158 mL |
| 140 kg | 42 mL | 85 mL | 127 mL | 170 mL |
* Derived using a slope of 3.3 kg/dL
Example 1: A patient with a body weight of 80 kg has a measured IgG trough level of 800 mg/dL and the reference trough level is 1000 mg/dL. The trough level difference is 200 mg/dL (1000 mg/dL minus 800 mg/dL). The dose of HYQVIA would be increased by 48 mL (4.8 grams) per dosing interval.
Example 2: A patient with a body weight of 60 kg has a measured IgG trough level of 1000 mg/dL and the reference trough level is 900 mg/dL. The trough level difference is -100 mg/dL (900 mg/dL minus 1000 mg/dL). The dose of HYQVIA would be decreased by 18 mL (1.8 grams) per dosing interval.
HYQVIA can be used to administer a full therapeutic dose in one site up to every four weeks. Adjust the frequency and number of infusion sites taking into consideration volume, total infusion time, and tolerability. Adjust the frequency as needed so that the patient receives the same weekly equivalent dose.
Example 3: When adjusting a dose of 30 grams administered every 3 weeks, administer 40 grams of HYQVIA every 4 weeks. If a higher trough level is required relative to intravenous treatment at 3- or 4-week intervals, increase the dose or decrease the dosing interval. Evaluate the use of a second site or infusing at shorter intervals when the volume of HYQVIA is greater than 600 mL.
If a patient misses a dose, administer the missed dose as soon as possible and then resume scheduled treatments as applicable.
If HYQVIA is administered at a different interval than the previous treatment, either intravenously or subcutaneously, then Table 2 should not be used and the dose of HYQVIA should be adjusted, if necessary, based on clinical response.
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
General instruction:
For patients switching from Immune Globulin Intravenous (Human) [IGIV] treatment:
2 Variations in the dosing interval of up to ±7 days or monthly equivalent dose amount of up to ±20% between the subject’s IgG infusions are considered a stable dose.
| Week* | Infusion Number | Dose Interval | Example for 100 g every 4 weeks |
|---|---|---|---|
| 1 | No infusion | Not applicable (NA) | NA |
| 2 | 1st infusion | 1-week-dose | 25g |
| 3 | 2nd infusion | 1-week-dose | 25g |
| 4 | 3rd infusion | 2-week-dose | 50g |
| 5 | No infusion | NA | NA |
| 6 | 4th infusion | 3-week-dose | 75g |
| 7 | No infusion | NA | NA |
| 8 | No infusion | NA | NA |
| 9 | 5th infusion | 4-week-dose | 100g (Full dose reached) |
* Clock starts one week after the last IGIV dose is administered. Week 1 is the week that starts one week after the last IGIV dose.
HYQVIA should be administered by a healthcare professional, caregiver or self-administered by the patient after appropriate training.
Selection of Infusion Site(s)
The suggested site(s) for the infusion of HYQVIA are the abdomen and thighs. If two sites are used, the two infusion sites should be on opposite sides of the body. If using three infusion sites, the sites should be at least 10 cm apart. Avoid bony prominences, or areas that are scarred, inflamed, or infected.
Volume per Site
Primary immunodeficiency (PI)
Administer up to 600 mL per site for patients whose body weight is greater than or equal to 40 kg and up to 300 mL per site for patients whose body weight is less than 40 kg.
A second site can be used at the discretion of the physician and patient based on tolerability and total volume. If a second site is used, administer half the total volume of rHuPH20 of HYQVIA in each site.
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
On a given infusion day, the maximum infusion volume should not exceed 1200 mL for patients weighing ≥40 kg or 600 mL for patients weighing <40 kg. If the maximum daily dose limit is exceeded or the patient cannot tolerate the infusion volume, the dose may be administered over multiple days in divided doses with 48 to 72 hours between doses to allow absorption of infusion fluid at the infusion site(s). The dose can be administered at 1, 2, or 3 infusion sites with a maximum infusion volume of 600 mL per site (or as tolerated). If using three sites, the maximum is 400 mL per site.
Rate of Infusion
Primary immunodeficiency (PI)
Administer the rHuPH20 of HYQVIA at an initial rate per site of approximately 1 to 2 mL per minute, or as tolerated.
Administer Immune Globulin Infusion (Human), 10% of HYQVIA at rates as shown in Table 4 for the initial infusions. If the patient tolerates these infusions at the full dose and maximum rate, adjust both the time intervals and number of rate changes of the ramp-up used for successive infusions at the discretion of the physician and patient.
| First 2 Infusions | Subsequent 2 or 3 Infusions | |||
|---|---|---|---|---|
| Patients <40 kg (<88lbs) | Patients ≥40 kg (≥88lbs) | Patients <40 kg (<88lbs) | Patients ≥40 kg (≥88lbs) | |
| Intervals | Rate per site | Rate per site | Rate per site | Rate per site |
| Minutes | mL per hour | mL per hour | mL per hour | mL per hour |
| 5 - 15 | 5 | 10 | 10 | 10 |
| 5 - 15 | 10 | 30 | 20 | 30 |
| 5 - 15 | 20 | 60 | 40 | 120 |
| 5 - 15 | 40 | 120 | 80 | 240 |
| Remainder of infusion | 80 | 240 | 160 | 300 |
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
The full dose of rHuPH20 solution is infused at a rate of 1 to 2 mL per minute (60 mL to 120 mL/hr) per infusion site or as tolerated. Immune Globulin Infusion, (Human), 10% can be administered through the same subcutaneous needle set within approximately 10 minutes after the rHuPH20 infusion is completed.
Patients with body weight of 40 kg or above
The Immune Globulin Infusion (Human), 10% should be infused at an initial rate of 10 mL per hour per infusion site. If tolerated, the rate of the administration may be increased at intervals of 5 to 15 minutes and to a maximum infusion rate of 240 mL per hour per infusion site for the initial one or two infusions. For subsequent infusions the rate can be adjusted to a maximum of 300 mL per hour per infusion site.
Patients with body weight under 40 kg
The Immune Globulin Infusion, (Human), 10% should be infused at an initial rate of 5 mL per hour per infusion site. If well tolerated, the rate of the administration may be increased at intervals of 5 to 15 minutes and to a maximum infusion rate of 80 mL per hour per infusion site for the initial one or two infusions. For subsequent infusions the rate can be adjusted to a maximum of 160 mL per hour per infusion site.
Instructions for Administration
To administer HYQVIA using the FDA-cleared Vial Access Devices (VAD), refer to the Instructions For Use (IFU) provided with the VAD. Note: Use the VAD to administer HYQVIA in adult patients only.
To administer HYQVIA using a needle or needle-less transfer device, refer to the following instructions below.
Use aseptic techniques when preparing and administering HYQVIA for infusion.
For more detail on steps, see accompanying Information for Patients.
1. Inspect the vials: Inspect for clarity, color, and expiration date(s).
2. Prepare for infusion:
3. Prepare the rHuPH20 of HYQVIA (Labeled as “HY”):
|
|
rHuPH20 may be delivered using the push method or via the pump method.
If using the pump method:
4. Prepare Immune Globulin Infusion (Human), 10% of HYQVIA (Labeled as “IG”):
If using the pump method:
If using a syringe driver method:
|
5. Prepare the infusion site(s):
|
|
6. Insert and secure the 24-gauge subcutaneous needle:
|
|
7. Administer the rHuPH20 of HYQVIA:
8. Administer the Immune Globulin Infusion (Human), 10% of HYQVIA:
Within approximately 10 minutes of completing the infusion of the rHuPH20 of HYQVIA, start the variable rate program of the infusion pump to initiate the infusion of the full therapeutic dose of Immune Globulin Infusion (Human), 10% of HYQVIA. At the end of the infusion, flush the infusion tubing up to the needle hub with normal saline or Dextrose 5% in water (D5W).
9. Remove subcutaneous needle(s) from the infusion site(s):
After the infusion is complete, remove the needle set and cover with a protective dressing. Discard any partially used vial(s) and disposable supplies in accordance with local requirements.
10. Document the infusion:
Remove the peel-off label from each Immune Globulin Infusion (Human), 10% vial of HYQVIA used and affix to the patient’s treatment record or infusion log. In addition, record the time, date, dose, infusion site location and any reactions after each infusion.
For self-administration, provide the patient with instructions and training for infusion in the home or other appropriate setting.
HYQVIA is a dual vial unit consisting of one vial of a liquid solution containing Immune Globulin Infusion (Human), 10% and one vial of a liquid solution containing 160 U/mL rHuPH20.
HYQVIA is available in the following strengths:
| Immune Globulin Infusion (Human), 10% | rHuPH20 | ||
|---|---|---|---|
| Volume | Grams Protein | Volume | Units |
| 25 mL | 2.5 | 1.25 mL | 200 |
| 50 mL | 5.0 | 2.5 mL | 400 |
| 100 mL | 10.0 | 5.0 mL | 800 |
| 200 mL | 20.0 | 10.0 mL | 1600 |
| 300 mL | 30.0 | 15.0 mL | 2400 |
HYQVIA is contraindicated in:
Severe hypersensitivity reactions may occur after treatment with immune globulin products, including HYQVIA, even in patients previously treated with immune globulin products. In case of hypersensitivity, discontinue the HYQVIA infusion immediately and institute appropriate treatment.
Immune Globulin Infusion (Human), 10% of HYQVIA contains IgA (average concentration of 37µg/mL). Patients with antibodies to IgA potentially are at greater risk of developing potentially severe hypersensitivity and anaphylactic reactions.
Thrombosis has been reported to occur following treatment with immune globulin products, including HYQVIA. 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.
Ensure adequate hydration in patients before administration of HYQVIA. For patients at risk of thrombosis, administer HYQVIA at the minimum dose and infusion rate practicable. Monitor patients for signs and symptoms of thrombosis.
Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, such as those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies. [see Boxed Warning, Dosage and Administration (2)].
Eighteen percent (15 of 83) of patients receiving HYQVIA in PID clinical studies developed non-neutralizing antibodies to the rHuPH20 component. The potential exists for such antibodies to cross-react with endogenous Hyaluronidase (PH20), which is known to be expressed in the adult male testes, epididymis, and sperm. It is unknown whether these antibodies can interfere with fertilization in humans. The clinical significance of these antibodies is not known.
Clinical studies in CIDP based on 4,729 rHuPH20 infusions in 132 patients revealed three incidences in two subjects of anti-rHuPH20 neutralizing antibody positivity. Elevation in neutralizing antibody titers was transient and occurred at three measurements over a 6-year follow-up period. No efficacy or safety issues were identified with the occurrence of neutralizing antibody positivity.
Aseptic meningitis syndrome (AMS) may occur with immune globulin products, including HYQVIA. Signs and symptoms of AMS include severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea and vomiting. AMS usually begins within several hours to 2 days following immune globulin treatment. Conduct neurological examination on patients exhibiting symptoms and signs of AMS, including Cerebrospinal fluid (CSF) studies, to rule out other causes of meningitis. CSF studies frequently reveal pleocytosis up to several thousand cells per cubic millimeter, elevated protein levels up to several hundred mg/dL, and negative culture results. Discontinuation of IgG treatment has resulted in remission of AMS within several days without sequelae.
Hemolysis may occur with immune globulin products, including HYQVIA due to the presence of blood group antibodies that may act as hemolysins and induce in vivo coating of red blood cells (RBC). This may cause a positive direct antiglobulin test [DAT (Coombs test)]. Delayed hemolytic anemia can develop after HYQVIA therapy due to enhanced RBC sequestration [see Adverse Reactions (6)].
Monitor patients for signs and symptoms of hemolysis. If signs and symptoms of hemolysis are observed, perform additional confirmatory laboratory testing.
Renal injury including acute renal failure, acute tubular necrosis, proximal tubular nephropathy, and osmotic nephrosis may occur after treatment with immune globulin products, including HYQVIA.
Ensure patients are not volume depleted before administering HYQVIA. In patients who are at risk of renal injury because of pre-existing renal insufficiency or predisposition to acute renal failure (such as diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs, etc.), administer HYQVIA at the minimum rate of infusion practicable [see Dosage and Administration (2.3)].
Assess renal function, including measurement of blood urea nitrogen (BUN), serum creatinine, and urine output in patients receiving HYQVIA prior to initial infusion and at appropriate intervals thereafter. If renal function deteriorates, consider discontinuation of HYQVIA [see Dosage and Administration (2.3)].
Infusion into or around an infected area can spread a localized infection. Do not infuse HYQVIA into these areas due to potential risk of spreading a localized infection.
Transfusion-Related Acute Lung Injury (TRALI) may occur with intravenously administered immune globulin products symptoms typically occur within 1 to 6 hours after treatment and may include severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever.
Monitor patients for signs and symptoms of TRALI. If TRALI is suspected, conduct an evaluation, including appropriate tests for the presence of anti-neutrophil and anti-HLA antibodies in both the product and patient serum. Manage patients using oxygen therapy with ventilatory support as appropriate.
There is risk of transmission of infectious disease or agents including viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and the Creutzfeldt-Jakob disease agent with HYQVIA administration because it is manufactured using human blood. The risk of infectious agent transmission is minimized by plasma donor screening, donation testing, and manufacturing steps proven to inactivate and remove bloodborne pathogens.
Report all infections thought to be possibly transmitted by HYQVIA to Takeda Pharmaceuticals U.S.A., Inc. at 1-877-TAKEDA-7 (1-877-825-3327) (In the U.S.).
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in clinical studies of a product cannot be directly compared to rates in the clinical studies of another product and may not reflect the rates observed in clinical practice.
Primary Immunodeficiency (PI)
Immune Globulin Infusion (Human), 10% administered intravenously: Prior to initiation of treatment with HYQVIA, 87 patients received 365 infusions of Immune Globulin Infusion (Human), 10% encompassing 22.2 patient-years. Among the 87 patients treated, 56 (64.4%) experienced 1 or more adverse reactions. Among the 365 intravenous infusions, 158 adverse reactions occurred for a rate per infusion of 0.43.
A total of 1,359 infusions of HYQVIA were administered during the trial; 230 of these infusions occurred during the ramp-up period and the other 1,129 occurred during the observation period. During the observation period, 81 patients received 1,129 infusions of HYQVIA; of those, 67 (82.7%) experienced one or more adverse reactions. Among the 1,129 HYQVIA infusions, 456 adverse reactions occurred for a rate per infusion of 0.40. Seven of these adverse reactions were severe, defined as marked impairment of function, can lead to temporary inability to resume normal life pattern, requires prolonged intervention and/or results in sequelae.
Adverse reactions occurring in greater than 5% of patients associated with infusions of HYQVIA vs. Immune Globulin Infusion (Human), 10% given intravenously are shown in Table 6. The majority of these adverse reactions was mild to moderate in severity and did not necessitate discontinuing the infusions. Mild is defined as transient discomfort that resolves spontaneously or with minimal intervention; moderate is defined as limited impairment of function that resolves spontaneously or with minimal intervention with no sequelae. No serious adverse reactions occurred during the HYQVIA clinical trials.
| HYQVIA | IGIV Given Intravenously | |||
|---|---|---|---|---|
| Adverse Reactions† | Number of Patients (%) N= 81 | Number of Adverse Reactions per Infusion (Rate‡) N = 1129 | Number of Patients (%) N=87 | Number of Adverse Reactions per Infusion (Rate) N = 365 |
| Local ARs | 42 (51.9%) | 234 (0.21) | 4 (4.6%) | 4 (0.01) |
| Systemic ARs | 55 (67.9%) | 222 (0.20) | 54 (62.1%) | 154 (0.42) |
| Headache | 17 (21%) | 40 (0.04) | 22 (25.3%) | 42 (0.12) |
| Fatigue | 9 (11.1%) | 16 (0.01) | 8 (9.2%) | 10 (0.03) |
| Nausea | 6 (7.4%) | 12 (0.01) | 10 (11.5%) | 10 (0.03) |
| Pyrexia | 6 (7.4%) | 11 (0.01) | 6 (6.9%) | 7 (0.02) |
| Vomiting | 6 (7.4%) | 11 (0.01) | 5 (5.7%) | 7 (0.02) |
* Causally related adverse events and/or temporally associated adverse events occurring within 72 hours.
† Excluding infections
‡ Rate= total number of events divided by total number of infusions.
Six patients, 2 children and 4 adults, withdrew from the trial during the efficacy treatment period with HYQVIA due to mild to moderate adverse reactions. One child withdrew due to local pain and one due to fever, vomiting, and headaches. Of the four adults, two withdrew due to local pain and swelling, one had moderate swelling that transiently extended from the abdominal infusion site to the genitalia, and one had back injury.
Antibodies binding to rHuPH20: A total of 15 out of 83 patients in the clinical trial who were treated with HYQVIA developed an antibody capable of binding to rHuPH20. These antibodies were not capable of neutralizing rHuPH20.
In the clinical trial, no temporal association between adverse reactions and the presence of antibodies capable of binding to the Recombinant Human Hyaluronidase of HYQVIA could be demonstrated. There was no increase in the incidence or severity of adverse reactions in patients who developed antibodies to rHuPH20 of HYQVIA. In all patients, antibody titers decreased despite continued treatment.
The effect of exposure to antibodies capable of binding to rHuPH20 of HYQVIA for periods longer than this clinical trial has not been evaluated.
The local adverse reactions are listed by frequency in Table 7. Mild swelling around the infusion site was present in most infusions due to the large volumes infused, but in general it was not considered to be an adverse reaction unless it caused discomfort. Among the 234 local adverse reactions, three were severe (infusion site pain, infusion site swelling and infusion site edema that extended from the abdominal infusion site to the genitalia); all were transient and resolved without sequelae. More than 98% of local reactions were either mild (70.5%) or moderate (28.2%) in severity.
| Infusion Site Reaction | Number and Rate of Reactions per Infusion (N=1129) |
|---|---|
| Rate per infusion = total number of events divided by total number of infusions. | |
| Discomfort/pain | 122 (0.11) |
| Erythema | 32 (0.03) |
| Swelling/Edema | 35 (0.03) |
| Pruritus | 22 (0.02) |
During the combined efficacy and extension trials encompassing more than 3 years, the local adverse reaction rate was 2.6 per patient-year. During the first 12-month period (months 1- 12), the rate was 3.68 local adverse reactions per patient-year. During the subsequent 12-month period (months 13-24), the rate declined to 2.12 local adverse reactions per-patient year. Finally, during the third 12-month period (months 25-36), the rate further declined to 0.37 local adverse reactions per patient-year.
Sixty-six of the 68 patients who completed the efficacy clinical trial enrolled in a prospective, open-label, multicenter extension trial to assess the long-term safety and tolerability of HYQVIA. Sixty-three of 66 patients enrolled received HYQVIA and 3 received IGIV. Of the 63 patients who received HYQVIA, 48 completed the extension trial. The cumulative exposure of HYQVIA across the two trials was 188 subject-years and 2,959 infusions, and a maximum exposure of 188 weeks or up to approximately 3.5 years. There were no clinically observable changes in the skin or subcutaneous tissue in either the efficacy or extension clinical trials.
Pediatric population in PI:
HYQVIA was evaluated in a pivotal efficacy and safety study in 44 pediatric patients (aged 2 to 16 years of age). Results from the interim data analysis, where all patients completed 12 months of participation (one year of observation period) in the study, indicated similar safety profiles to adults [see Clinical Pharmacology (12.3), and Clinical Studies (14.1)].
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
The safety of HYQVIA in adult patients with CIDP was evaluated in 104 unique patients in a randomized, placebo-controlled study (Study 1) and a single-arm, open-label, extension study (Study 2). A total of 4085 infusions of HYQVIA were administered during these 2 studies [see Clinical Studies (14.2)].
Development of antibodies to rHuPH20: A total of 15 patients (14.4%) who were treated with HYQVIA in Studies 1 and 2 developed high-binding anti-rHuPH20 antibody titers (≥1:160). A total of 7 patients (11.3%) who were treated with HYQVIA in Study 1 and a total of 14 patients (16.7%) in Study 2 developed high-binding anti-rHuPH20 antibodies (≥1:160). Of the 7 patients in Study 1, 6 continued to have high-binding antibodies in Study 2, and 1 subject did not enter Study 2. Eight of the 14 patients developed high-binding antibodies during Study 2. The occurrence of high-binding antibodies was not associated with an increased rate of TEAEs. Two subjects had a transient positivity of neutralizing antibodies which were not associated with any TEAE consistent with decreased rHuPH20 effect (in Study 2). The binding antibody positivity rate was comparable to the rates reported in other development programs.
Study 1
A total of 62 patients received HYQVIA and a total of 598 infusions of HYQVIA were administered. Adverse reactions (ARs) occurring in >5% of patients with CIDP treated with HYQVIA in Study 1 are shown in Table 8.
| ARs† | HYQVIA Number of Patients (%) N = 62 | HYQVIA Number of ARs per Infusion (Rate‡) N = 598 | Placebo Number of Patients (%) N=70 | Placebo Number of ARs per Infusion (Rate‡) N=644 |
|---|---|---|---|---|
| AR=adverse reactions | ||||
| • Local ARs | 17 (27.4) | 103 (0.17) | 5 (7.1) | 13 (0.02) |
| • Systemic ARs | 18 (29.0) | 44 (0.07) | 7 (10.0) | 14 (0.02) |
| - Nausea | 7 (11.3) | 8 (0.01) | 0 | 0 |
| - Fatigue | 5 (8.1) | 7 (0.01) | 1 (1.4) | 1 (<0.01) |
| - Pruritus | 5 (8.1) | 14 (0.02) | 1 (1.4) | 1 (<0.01) |
| - Headache | 4 (6.5) | 9 (0.02) | 5 (7.1) | 12 (0.02) |
| - Pyrexia | 4 (6.5) | 6 (0.01) | 0 | 0 |
* Causally related adverse events and/or temporally associated adverse events occurring within 72 hours.
† Excluding infections
‡ Rate=total number of events divided by total number of infusions.
Blood pressure elevation was reported in 4 patients (6.5%) treated with HYQVIA in this study, including 2 patients with a history of hypertension on antihypertensive medications. Three of the 4 patients had events which were causally related and/or temporally associated (occurring within 72 hours).
A total of 4 patients (3.0%) experienced adverse events (AEs) that led to discontinuation from the study; Three (3) patients in the HYQVIA group and 1 in the placebo group. The AEs leading to discontinuation in the 3 HYQVIA patients included: a cerebrovascular accident in 1 subject (who had coexisting cardiovascular risk factors), infusion site edema and infusion site pain in another subject, and nausea and chills in the third subject.
The most frequent local ARs in Study 1 are listed by frequency in Table 9. All HYQVIA local reactions (100%) were either mild (88.41%) or moderate (11.59%) in severity.
| Infusion Site Reaction | HYQVIA Number of ARs per Infusion (%) N = 598 | Placebo Number of ARs per Infusion (%) N = 644 |
|---|---|---|
| AR=adverse reaction | ||
| Discomfort/pain | 39 (6.5%) | 12 (1.9%) |
| Swelling/edema | 38 (6.4%) | 6 (0.9%) |
| Erythema | 36 (6.0%) | 0 |
| Pruritus | 15 (2.5%) | 0 |
Study 2
A total of 85 patients received HYQVIA and a total of 3,487 infusions of HYQVIA were administered. Adverse reactions occurring in >5% of patients with CIDP treated with HYQVIA in Study 2 are shown in Table 10.
| ARs† | Number of Patients (%) N = 85 | Number of ARs per Infusion (Rate‡) N = 3,487 |
|---|---|---|
| AR=adverse reactions | ||
| • Local ARs | 16 (18.8) | 362 (0.10) |
| • Systemic ARs | 27 (31.8) | 197 (0.06) |
| - Headache | 17 (20.0) | 78 (0.02) |
| - Pyrexia | 12 (14.1) | 58 (0.02) |
| - Nausea | 7 (8.2) | 9 (<0.01) |
| - Fatigue | 6 (7.1) | 9 (<0.01) |
| - Erythema | 5 (5.9) | 43 (0.01) |
* Causally related adverse events and/or temporally associated adverse events occurring within 72 hours.
† Excluding infections
‡ Rate=total number of events divided by total number of infusions.
Blood pressure elevation was reported in 9 patients (10.6%) in this study, including 1 subject with a history of hypertension on antihypertensive medications. Two (2) of the 9 patients had an event which was causally related and/or temporally associated (occurring within 72 hours).
A total of 4 patients (4.7%) experienced AEs that led to discontinuation from the study and 1 subject (1.3%) died prior to the time of the interim analysis. The AEs leading to discontinuation in the 4 patients included mantle cell lymphoma in 1 subject, muscular weakness and worsening of CIDP in another subject, abdominal pain in the third subject, and hypoventilation in the fourth subject. The cause of death in the 1 subject was cholangiocarcinoma.
The most frequent local ARs in Study 161505 are listed by frequency in Table 11. Most of the local reactions (96.4%) were either mild (88.4%) or moderate (8.0%) in severity.
| Infusion Site Reaction | Number of ARs per Infusion (%) N = 3,487 |
|---|---|
| AR=adverse reaction | |
| Erythema | 366 (10.5%) |
| Swelling/edema | 76 (2.2%) |
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.
In addition to the adverse reactions listed above in clinical trials, the following adverse reactions have been reported in the postmarketing experience:
Immune System Disorder: Hypersensitivity
General Disorder and Administration Site Conditions: Influenza-like illness, Infusion site leaking
Postmarketing Experience of Immune Globulin Products
The following adverse reactions have been identified and reported during the postmarketing use of Immune Globulin products administered subcutaneously:
Anaphylactic reaction, Tremor, Tachycardia, Hypotension, Infusion related reaction, Dyspnea, Paresthesia oral, Dermatitis allergic, Injection site rash, and Alanine aminotransferase increased.
Passive transfer of antibodies can transiently impair the immune responses to live attenuated virus vaccines, such as mumps, rubella, and varicella for up to 6 months and for a year or more to measles.
Admixtures of HYQVIA with other drugs solutions have not been evaluated. Do not mix or administer components of HYQVIA with other products.
Risk Summary
Limited human data are available to assess the presence or absence of drug-associated risk in pregnancy. In a postmarketing pregnancy study, two out of 5 infants born to mothers taking HYQVIA during pregnancy had congenital abnormalities (1 cleft lip and 1 talipes calcaneovalgus). Animal reproduction studies have not been conducted with the Immune Globulin Infusion (Human), 10% component of HYQVIA. Immune globulins increasingly cross the placenta from maternal circulation after 30 weeks of gestation. There was no evidence of teratogenicity in animal studies for rHuPH20, (a component of HYQVIA). The effects of antibodies to the rHuPH20 on the human embryo or fetal development are unknown. It is not known whether HYQVIA can cause fetal harm when administered to a pregnant woman or if it can affect reproductive capacity. HYQVIA should be given to a pregnant woman only if clearly needed.
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 background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Human data:
Nine women treated with HYQVIA were enrolled in a prospective, uncontrolled, open-label, multicenter post-authorization Pregnancy Registry. Seven mothers continued HYQVIA, and two mothers were treated with immune globulin other than HYQVIA during the pregnancy. One mother discontinued from the registry before the expected delivery. Of the eight pregnancies with known outcomes, there were eight live births. There were no specified labor or delivery complications. Two out of 5 infants whose mothers took HYQVIA during pregnancy had congenital abnormalities (cleft lip without cleft palate and talipes calcaneovalgus). Data from the HYQVIA Pregnancy Registry are insufficient to establish causality. The interpretation of the registry findings is limited by the small sample size, by the potential that selection bias may have increased enrollment of mothers of infants with congenital abnormalities, the absence of fetal outcomes in some exposed maternal-fetal pairs, and incomplete data on other potential etiologies.
The following adverse events were identified in post-approval reports: spontaneous abortions and fetal deaths. The following congenital anomalies were identified in post-approval reports in infants whose mothers took HYQVIA during pregnancy: cleft palate, atrial septal defect, ventricular septal defect, cleft lip, hypoplastic left heart syndrome (aortic atresia, mitral valve atresia), endocardial fibroelastosis, and tricuspid valve incompetence. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Animal data:
Animal reproduction studies have not been conducted with Immune Globulin Infusion (Human), 10% component of HYQVIA.
Development and reproductive toxicology studies have been conducted with rHuPH20 in mice and rabbits [see Nonclinical Toxicology (13.2)]. No adverse effects on pregnancy were associated with anti-rHuPH20 antibodies at a dose of 3 mg/kg rHuPH20 in mice, which is 4,800 times higher than the typical monthly human dose. No teratogenicity or signs of maternal toxicity were observed at doses up to 18 mg/kg, which is 28,800 times higher than the typical monthly human dose. Doses of 9 and 18 mg/kg (14,400 and 28,800 times higher than the typical monthly human dose) in mice were associated with reduced fetal weight and an increased number of fetal resorptions. In these studies, maternal antibodies to rHuPH20 were transferred to offspring in utero. The effects of antibodies to the rHuPH20 component of HYQVIA on the human embryo or on human fetal development are unknown.
Risk Summary
It is not known whether HYQVIA can cause harm to the breastfed infant when administered to a lactating woman. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for HYQVIA and any potential adverse effects on the breastfed infant from HYQVIA or from the underlying maternal condition. Data from the HYQVIA Pregnancy Registry are insufficient to predict effects on the breastfed child from exposure to HYQVIA through human milk.
Data
Animal data:
In animal studies, maternal antibodies binding to rHuPH20 were transferred to offspring during lactation. No adverse effects on pregnancy or offspring development were associated with anti-rHuPH20 antibodies. The effects of antibodies that bind to rHuPH20 of HYQVIA transferred during human lactation are unknown.
Risk Summary
Animal studies do not indicate direct or indirect harmful effects of (rHuPH20) with respect to reproductive potential at the doses used for facilitating administration of IG 10% [see Nonclinical Toxicology (13.1)].
Primary Immunodeficiency (PI)
The safety and effectiveness of HYQVIA for the treatment of Primary Immunodeficiency have been established in pediatric patients 2 years and older.
Use of HYQVIA for this indication is supported by evidence from the pivotal efficacy and safety study in 44 pediatric patients (aged 2 to 16 years of age). Results from pre-specified interim data analysis, where all patients completed 12 months of participation (one year of observation period) in the study, indicated similar safety profiles to adults. No pediatric-specific dose requirements were necessary to achieve the desired serum IgG levels. [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.1)].
Safety and effectiveness of HYQVIA has not been evaluated in patients <2 years of age.
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
The safety and effectiveness of HYQVIA for the treatment of CIDP have not been established in pediatric patients.
Primary Immunodeficiency (PI)
HYQVIA was evaluated in 7 patients over age 65 in the PI clinical trial. The available data are too limited to draw safety conclusions.
Chronic Inflammatory Demyelinating Polyneuropathy
HYQVIA was evaluated in 13 patients over age 65 in the pivotal clinical trial. No clinically significant differences in safety were observed between those 13 elderly patients and the patients 18 to 65 years of age.
Use caution when administering HYQVIA to patients age 65 and over who are judged to be at increased risk of developing thrombosis and acute renal insufficiency [see Boxed Warning, Warnings and Precautions (5.2, 5.6)]. Do not exceed recommended doses and administer HYQVIA at the minimum dose and infusion rate practicable.
HYQVIA is a dual vial unit with one vial of Immune Globulin Infusion (Human), 10% and one vial of rHuPH20.
The Immune Globulin Infusion (Human), 10% of HYQVIA is a ready-for-use, sterile, liquid preparation of highly purified and concentrated IgG antibodies. The distribution of the IgG subclasses is similar to that of normal plasma. The Fc and Fab functions are maintained in the primary component. Pre-kallikrein activator activity is not detectable. The Immune Globulin Infusion (Human), 10% of HYQVIA contains 100 mg/mL protein. At least 98% of the protein is IgG, average immunoglobulin A (IgA) concentration is 37µg/mL, and immunoglobulin M (IgM) is present in trace amounts. The Immune Globulin Infusion (Human), 10% of HYQVIA contains a broad spectrum of IgG antibodies against bacterial and viral agents. Glycine (0.25M) serves as a stabilizing and buffering agent. There is no added sugar, sodium, or preservatives. The pH is 4.6 to 5.1. The osmolality is 240 to 300 mOsmol/kg.
The Immune Globulin Infusion (Human), 10% of HYQVIA is manufactured from large pools of human plasma. IgG preparations are purified from plasma pools using a modified Cohn-Oncley cold ethanol fractionation process, as well as cation and anion exchange chromatography.
Screening against potentially infectious agents begins with the donor selection process and continues throughout plasma collection and plasma preparation. Each individual plasma donation used in the manufacture of the Immune Globulin Infusion (Human), 10% of HYQVIA is collected only at FDA approved blood establishments and is tested by FDA licensed serological tests for Hepatitis B Surface Antigen (HBsAg), and for antibodies to Human Immunodeficiency Virus (HIV-1/HIV-2) and Hepatitis C Virus (HCV) in accordance with U.S. regulatory requirements. As an additional safety measure, mini-pools of the plasma are tested for the presence of HIV-1 and HCV by FDA licensed Nucleic Acid Testing (NAT).
To further improve the margin of safety, three dedicated, independent and effective virus inactivation/removal steps have been integrated into the manufacturing and formulation processes, namely solvent/detergent (S/D) treatment, 35 nm nanofiltration, and a low pH incubation at elevated temperature. The S/D process includes treatment with an organic mixture of tri-n-butyl phosphate, octoxynol 9 and polysorbate 80 at 18°C to 25°C for a minimum of 60 minutes.
In vitro virus spiking studies have been used to validate the capability of the manufacturing process to inactivate and remove viruses. To establish the minimum applicable virus clearance capacity of the manufacturing process, these virus clearance studies were performed under extreme conditions (e.g., at minimum S/D concentrations, incubation time and temperature for the S/D treatment). Virus clearance studies for the Immune Globulin Infusion (Human), 10% of HYQVIA performed in accordance with good laboratory practices (Table 12) have demonstrated that:
| Virus type | Enveloped RNA | Enveloped DNA | Non-enveloped RNA | Non-enveloped DNA | |||
|---|---|---|---|---|---|---|---|
| Family | Retroviridae | Flaviviridae | Herpesviridae | Picornaviridae | Parvoviridae | ||
| Virus | HIV-1 | BVDV | WNV | PRV | HAV | EMCV | MMV |
| Abbreviations: HIV-1, Human Immunodeficiency Virus Type 1; BVDV, Bovine Viral Diarrhea Virus (model for Hepatitis C Virus and other lipid enveloped RNA viruses); WNV, West Nile Virus; PRV, Pseudorabies Virus (model for lipid enveloped DNA viruses, including Hepatitis B Virus); EMCV, Encephalomyocarditis Virus (model for non-lipid enveloped RNA viruses, including Hepatitis A virus [HAV]); MMV, Mice Minute Virus (model for non-lipid enveloped DNA viruses, including B19 virus [B19V]); n.d. (not done), n.a. (not applicable). | |||||||
| SD treatment | >4.5 | >6.2 | n.a. | >4.8 | n.d. | n.d. | n.d. |
| 35 nm nanofiltration | >4.5 | >5.1 | >6.2 | >5.6 | 5.7 | 1.4 | 2.0 |
| Low pH treatment | >5.8 | >5.5 | >6.0 | >6.5 | n.d.† | >6.3 | 3.1 |
| Overall log reduction factor (ORF) | >14.8 | >16.8 | >12.2 | >16.9 | 5.7 † | >7.7 | 5.1 |
* For the calculation of these RF data from virus clearance study reports, applicable manufacturing conditions were used. Log10 RFs on the order of 4 or more are considered effective for virus clearance in accordance with the Committee for Medicinal Products for Human Use (CHMP, formerly CPMP) guidelines.
† No RF obtained due to immediate neutralization of HAV by the anti-HAV antibodies present in the product.
The rHuPH20 of HYQVIA is produced from genetically engineered Chinese Hamster Ovary (CHO) cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase PH20. The purified hyaluronidase glycoprotein contains 447 amino acids with an approximate molecular weight of 61,000 Daltons [see Clinical Pharmacology (12.1)]. This component is supplied as a sterile, clear, colorless, ready-for-use solution and has an approximate pH of 7.4 and an osmolality of 290 to 350 mOsm. Each vial contains 160 U/mL of rHuPH20 with 8.5 mg/mL sodium chloride, 1.78 mg/mL sodium phosphate dibasic dihydrate, 1.0 mg/mL human albumin, 1.0 mg/mL edentate disodium dihydrate, 0.40 mg/mL calcium chloride dihydrate, and 0.17 mg/mL sodium hydroxide added for pH adjustment. It does not contain preservatives.
Due to comprehensive virus testing at the Master Cell Bank, Working Cell Bank and bulk harvest stage, effective virus reduction during the purification process and use of pharmaceutical grade human albumin as an excipient with no other materials of human or animal origin involved in the manufacturing process, rHuPH20 provides for high margins of safety with respect to viruses.
The Immune Globulin Infusion (Human), 10% provides the therapeutic effect of HYQVIA. The Recombinant Human Hyaluronidase of HYQVIA increases dispersion and absorption of the Immune Globulin Infusion (Human), 10%. The Immune Globulin Infusion (Human), 10% of HYQVIA supplies a broad spectrum of opsonizing and neutralizing IgG antibodies against a wide variety of bacterial and viral agents. The Immune Globulin Infusion (Human), 10% also contains a spectrum of antibodies capable of interacting with and altering the activity of cells of the immune system as well as antibodies capable of reacting with cells such as erythrocytes. The role of these antibodies and the mechanisms of action of IgG in the Immune Globulin Infusion (Human), 10% of HYQVIA have not been fully elucidated.
The mechanism of action of immunoglobulins in the treatment of CIDP in adults has not been fully elucidated but may include immunomodulatory effects.
Hyaluronan is a polysaccharide found in the extracellular matrix of connective tissue. It is depolymerized by the naturally occurring enzyme hyaluronidase. Unlike the stable structural components of the interstitial matrix, hyaluronan has a very fast turnover with a half-life of approximately 0.5 days. The rHuPH20 of HYQVIA increases permeability of the subcutaneous tissue by temporarily depolymerizing hyaluronan. In the doses administered, rHuPH20 of HYQVIA acts locally. The effects of the hyaluronidase are reversible, and permeability of the subcutaneous tissue is restored within 24 to 48 hours.
Primary Immunodeficiency (PI)
The pharmacokinetics (PK) of HYQVIA was evaluated during a clinical trial of adults with PI after they achieved steady state at their 3- or 4-week dosing interval and underwent individual dose adjustment [see Clinical Studies (14)]. For adults, dose adjustment was based on a comparison of the ratios of the area under the IgG concentration versus time curve (AUC) during intravenous treatment versus during HYQVIA treatment.
The AUC of HYQVIA compared to conventional IGSC administration was 20% higher. The bioavailability of HYQVIA based on weekly AUC was 93.3% relative to IGIV.
The pharmacokinetic parameters of HYQVIA compared with intravenously administered Immune Globulin Infusion (Human), 10% are shown in Table 13. The mean IgG dose in weekly equivalents was 147 mg/kg ± 50 (range 134 to 160 mg/kg). The serum IgG trough levels are comparable: the mean serum IgG trough with HYQVIA was 1077 mg/dL compared with 1095 mg/dL with intravenously administered Immune Globulin Infusion (Human), 10%. Cmax was lower with HYQVIA (1607 mg/dL) than with intravenously administered Immune Globulin Infusion (Human), 10% (2248 mg/dL). Time to reach maximum concentration of IgG following HYQVIA administration was 5 (3.3-5.1) days.
In the extension trial, reducing the dosing interval from 4 to 2 weeks resulted in a mean increase of 13% in serum IG trough levels.
| HYQVIA | IGIV | ||
|---|---|---|---|
| Number of Patients | 60 | 68 | |
| IgG Weekly Dose [mg/kg/week] | |||
| Mean (SD) | 147 (50) | 139 (55) | |
| 95% CI | 134 to 160 | 126 to 153 | |
| Cmax [mg/dL] | |||
| Mean (SD) | 1607 (382) | 2248 (547) | |
| 95% CI | 1508 to 1706 | 2116 to 2380 | |
| IgG Trough Levels [mg/dL]* | |||
| Mean (SD) | 1077 (275) | 1095 (321) | |
| 95% CI | 1004 to 1149 | 1017 to 1174 | |
| AUC/week [g*days/L]† | |||
| Mean (SD) | 91.4 (21) | 98.7 (24.3) | |
| 95% CI | 85.9 to 96.8 | 92.8 to 104.5 | |
| Bioavailability‡ | |||
| Point estimate | 93.3 | 100% (defined) | |
| 90% CI | 91.4 to 95.2 | N/A | |
| Clearance [mL/kg/day] | |||
| Mean (SD) | 1.6 (0.5)§ | 1.4 (0.4) | |
| 95% CI | 1.5 to 1.8 | 1.3 to 1.5 | |
| Terminal Half-life [days] | |||
| Mean (SD) | 59.3 (36.1) | 41.6 (26.9) | |
| 95% CI | 50 to 68.6 | 35.1 to 48.1 | |
| Tmax [days] | |||
| Median | 5.0 | 0.1 | |
| 95% CI | 3.3 to 5.1 | 0.1 to 0.1 | |
* N=58 for HYQVIA and N=67 for IGIV.
† Standardized to a 7-day interval.
‡ calculated based on weekly AUC; N=58 for HYQVIA.
§ Apparent clearance
Figure 1* shows a mean concentration-time plot of IgG in patients 12 years and older. The concentration-time profile of HYQVIA is similar to that of intravenous administration but without the high peak. The peak to trough variation is more similar to subcutaneous administration.
 |
* IGIV and HYQVIA data at 28-day dosing interval; IGSC data at 7-day dosing interval; IGSC dotted line shows weekly dose extrapolated over 21 additional days.
Pediatric Population
Results from the pivotal pediatric study suggest no clinically meaningful differences across age (2 to 16 years) groups with respect to total IgG PK (AUC/week and CL/F/BW) and serum trough levels.
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
The pharmacokinetic profile of HYQVIA was not evaluated in clinical study 1 in patients with CIDP aged 18 years and older. Serum trough levels of total IgG were assessed throughout the study 1. Trough-level data at baseline, interim visit, and end of study were presented in Table 14.
| Treatment Arm | Baseline * | Interim Visit † | End of Epoch 1 Treatment / Early Termination |
|---|---|---|---|
| SD = Standard deviation. N = Number of patients who had a value at each time point. | |||
| HYQVIA | |||
| N | 45 | 44 | 46 |
| Mean (SD) | 1465.3 (323.6) | 1487.1 (348.0) | 1569.5 (450.4) |
| Min, Max | 966, 2230 | 755, 2510 | 855, 2880 |
| Placebo | |||
| N | 55 | 40 | 55 |
| Mean (SD) | 1477.6 (356.9) | 1113.4 (275.9) | 1240.8 (574.3) |
| Min, Max | 655, 2870 | 449, 1690 | 449, 4680 |
Immune Globulin Infusion (Human), 10%
Long-term animal studies have not been conducted to evaluate the carcinogenic potential of Immune Globulin Infusion (Human), 10% or its effect on fertility.
An in vitro mutagenicity test was performed for Immune Globulin Infusion (Human), 10%. No evidence of mutagenicity was observed.
rHuPH20
Hyaluronidases are found in most tissues of the body. Long-term animal studies to evaluate the carcinogenic or mutagenic potential of rHuPH20 have not been conducted.
No adverse effects on fertility were observed in mice, rabbits and cynomolgus monkeys exposed to antibodies that bind to rHuPH20 and species-specific hyaluronidase. Reversible infertility has been observed in male and female guinea pigs immunized to produce antibodies to hyaluronidase. However, antibodies to hyaluronidase did not influence reproduction following immunization of mice, rabbits, sheep, or cynomolgus monkeys. The effects of antibodies that bind to rHuPH20 on human fertility are unknown.
Developmental studies in mice demonstrated that administration of rHuPH20 did not produce teratogenicity or signs of maternal toxicity at doses up to 18 mg/kg (2.2 × 106 U/kg), which is 28,800 times higher than the typical monthly human dose. Maternal doses of 9 and 18 mg/kg were associated with reduced fetal weight and an increased number of fetal resorptions. No adverse effects on fetal development were observed at a maternal dose of 3 mg/kg (360,000 U/kg) in mice and 0.76 mg/kg (91,000 U/kg) in rabbits, which is 4,800 and 1,200 times higher than the typical monthly human dose.
In a peri-and post-natal reproduction study, female mice were dosed daily with rHuPH20 from implantation through lactation and weaning. There were no adverse effects on gestation, parturition, lactation and maternal behavior or on the development of the male or female offspring of the treated female mice in terms of sexual maturation, learning and memory of offspring, or their ability to produce another generation of offspring at doses up to 9 mg/kg (1.1 ×106 Unit/kg), which is 14,400 times higher than the typical monthly human dose.
A prospective, open-label, non-controlled, multicenter trial was conducted in the US to determine the efficacy, tolerability, and pharmacokinetics (PK) of HYQVIA in patients with PI. Two cohorts of patients were enrolled. Thirty-one patients had been treated intravenously for three months and then subcutaneously each week at 137% of the intravenous dose for approximately one year before transitioning to the HYQVIA trial. The remaining patients also were treated intravenously for 3 months and then immediately began treatment with HYQVIA in the trial.
One week after the last intravenous or subcutaneous infusion, each subject began subcutaneous treatment with HYQVIA. After placing the subcutaneous needle set, the rHuPH20 of HYQVIA was infused through the needle set followed within 10 minutes by the immune globulin of HYQVIA at 108% of the intravenous dose. Dosing began with a 1-week equivalent dose. One week later, a 2-week dose was administered, followed 2 weeks later with a 3-week dose. For those patients who were on a 4-week dose interval prior to entering the trial, 3 weeks later the 4-week dose was administered. This ramp-up period allowed patients to become familiar with the large volumes required for a full 3- or 4-week treatment. Subsequently, patients continued the 3- or 4-week dosing for the remainder of the trial. After 3 doses at the full volume, a serum IgG trough level was obtained for all patients and used to individually adapt the subcutaneous dose of HYQVIA to compensate for individual variation from the mean value of 108% [see Clinical Pharmacology (12.3) and Administration (2.2)]. All patients who completed the trial received a minimum of 12 infusions at this individually adapted dose. The period after the ramp-up was considered the efficacy period and used for safety and efficacy analyses.
Outcome measures included the rate of infections, adverse reactions, tolerability of the infusions of HYQVIA, number of infusion sites per month, and infusion rate. Eighty-nine patients were enrolled, 87 treated intravenously and 83 treated with HYQVIA. The majority were Caucasian (79/87, 90.8%). Median age was 35.0 years (range 4 to 78 years). Forty-four of the patients were naïve to subcutaneous treatment. Median serum IgG trough levels for the 6 months before enrollment were 1033.5 mg/dL (range: 405 to 3200 mg/dL) in subcutaneous-experienced patients and 1000 mg/dL (range: 636 to 3200 mg/dL) in the subcutaneous-naïve patients.
The 83 patients received a total of 1,359 infusions of HYQVIA during the entire trial. Of these, 1,129 were administered after the ramp-up when the patients were on a consistent interval of 3 or 4 weeks, which was predetermined to be the efficacy period for data analysis.
Median duration of treatment in the IGIV period was 91 days (range 84 to 122 days). Median duration of HYQVIA treatment during the dose ramp up period was 42 days (range 20 to 49), and during the efficacy period was 366 days (range 42 to 507 days). None of the patients withdrew due to a severe or serious local or systemic adverse reaction [see Adverse Reactions (6.1)].
There were two acute serious bacterial infections (aSBI), both of which were episodes of pneumonia treated as outpatients with oral antibiotics during the 12-month efficacy period; an additional pneumonia requiring hospitalization occurred during the ramp-up. Based on this, the annualized rate of aSBI while treated with HYQVIA was 0.025, with an upper 99% confidence limit of 0.089, which is significantly less than (p<0.0001) the rate of one infection per year.
The overall rates of infections throughout both the efficacy and extension trials are shown in Table 15. The secondary endpoints evaluated in the efficacy trial were the annual rate of all infections and other efficacy measures.
| Annual Rate | ||
|---|---|---|
| Parameter | Mean | 95% CI |
| Infections per patient per year (Efficacy Trial) | 2.97 | 2.51 to 3.47 |
| Infections per patient per year (Efficacy and Extension Trials) | 2.99 | 2.60 to 3.42 |
| Days off school/work | 3.31 | 2.37 to 4.47 |
| Days on antibiotics | 20.26 | 15.45 to 25.98 |
| Unscheduled physician visits for infections | 4.78 | 3.83 to 5.88 |
| Days in hospital due to infection | 0.037 | 0.009 to 0.095 |
An objective of the trial was to achieve the same number or fewer infusions with HYQVIA per month as with intravenous administration and significantly fewer than with conventional subcutaneous administration. A summary of intravenous administration compared with HYQVIA administration is presented in Table 16.
| Parameter | Intravenous | HYQVIA |
|---|---|---|
| Median monthly number of infusion sites | 1.34 (1.2 to 1.7) | 1.09 (1.0 to 3.5) |
| Mean volume per site (mL) | 339 (75 to 800) | 292 (91 to 648) |
| Dose per site (g) | 33.9 (7.5 to 80.0) | 29.2 (9.1 to 64.8) |
| Median duration of individual infusions (hr) | 2.33 (0.92 to 6.33) | 2.08 (0.83 to 4.68) |
| Monthly median infusion time (hr/month) | 3.2 | 2.64 |
| Median maximum infusion rate (mL/hr) | 246 (60 to 668) | 300 (10 to 300) |
| Percent (%) of infusion completed without change in rate, interruption, and discontinuation | 95.9 | 97.7 |
Sixteen of 83 patients (19.3%) were infused every 3 weeks and 67 (80.7%) were infused every 4 weeks. Seventy-eight of 83 (94%) patients attained the same 3- or 4-week dosing as their previous IV treatment. One decreased from 4 to 3 weeks, one from 4 to 2 weeks and one from 3 to 2 weeks. The primary reason for decreasing the interval was discomfort due to swelling.
In a separate study evaluating subcutaneous treatment with Immune Globulin Infusion (Human), 10% a median of 21.43 sites were required each month with a median monthly infusion time of 5.35 hours.
Pediatric Study
A prospective, open-label, non-controlled, multicenter trial was conducted in the US to determine the efficacy, safety, immunogenicity and pharmacokinetics (PK) of HYQVIA in pediatric patients with PI who had received IVIG or SCIG treatment before enrollment into the trial. A total of 44 patients were enrolled, and the median age of pediatric patients was 9.5 years (range: 3 to 15 years). Of the enrolled patients, 26 patients (59.1%) were male, 18 patients (40.9%) were female, and 40 patients (90.9%) were White. Most patients were not Hispanic or Latino (39 patients [88.6%]).
Pediatric patients switched to HYQVIA SC immunoglobulin treatment schedule administered at doses (volumes and treatment intervals) typical for IVIG administration. Treatment intervals and doses gradually increased in a ramp-up phase to an interval of 3 or 4 weeks. Data were analyzed when all patients completed 12 months of participation (one year of observation) in the trial. Overall, the median number of infusions per month was 1.1 (range: 1.0 to 1.5) and was comparable across the age groups. The median number of infusion sites per month was 2.2 (range: 1.1 to 2.9), with a similar median number for all age categories. There were no clinically meaningful differences in trough IgG levels across age groups.
The primary analysis for efficacy was based on the rate of aSBIs, defined as bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess, per subject per year. Secondary analyses included the annual rate of other infections and health resource utilization outcome measures (e.g., days out of work/school/daycare).
During the 12-month trial period, the mean aSBI rate per year was 0.04 (with an upper 1-sided 99% confidence interval of 0.21, p<0.001), which met the predefined success rate of less than one aSBI per subject per year. One subject experienced two aSBIs of bacterial pneumonia, and there were no other episodes of serious bacterial infections reported in this trial. The mean rate of all infections per subject-year was 3.20, with an upper limit of the 95% CI of 4.05. The overall rate of infections per subject is consistent with results obtained in the pivotal clinical study. Pediatric patients missed a mean (95% CI) of 5.0 (2.2 to 7.9) days of work/school/daycare.
Safety and efficacy of HYQVIA in adult patients with CIDP was evaluated in a randomized, placebo-controlled study (Study 1) and a single-arm, open-label, extension study (Study 2).
Study 1:
In a multicenter, randomized, placebo-controlled, phase 3 study, 132 adult patients with CIDP underwent evaluation of safety and tolerability, 122 patients underwent efficacy evaluation of HYQVIA as a maintenance therapy to prevent relapse that allowed self-infusion of a total therapeutic dose every 2 to 4 weeks. The study enrolled patients ≥18 years of age (male or female) at the time of screening who had a documented diagnosis of definite or probable CIDP as per the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 criteria. All eligible patients had responded to IgG treatment in the past (partial or complete resolution of neurological symptoms and deficits) and were on a stable dose of IGIV treatment within the dose range equivalent to a cumulative monthly dose of 0.4 to 2.4 g/kg body weight administered intravenously for at least 12 weeks before screening. The primary endpoint was the proportion of patients who experienced a relapse, defined as an increase of ≥1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted inflammatory neuropathy cause and treatment (INCAT) disability scores obtained less than seven days apart.
Overall, a total of 184 patients were screened, of which 46 (25%) were screen failures, 138 (75%) were randomized, and 132 (71.7%) received either HYQVIA (N=62) or placebo (N=70), 17 discontinued in Epoch 1, and 94 completed the study without developing a relapse in Epoch 1 and 21 rolled over to Epoch 2. All 132 treated patients were analyzed for safety and 122 patients (N= 57 for HYQVIA, N=65 for placebo) were analyzed for efficacy included in the modified intent-to-treat (mITT). The mean duration of exposure was 5.3 months in the HYQVIA group and 4.7 months in the placebo group. The mean monthly equivalent dose was 1.1g/kg. The average time to deliver the monthly HYQVIA dose was approximately 2 hrs. HYQVIA infusions were administered through 1 to 3 injection sites, and the majority of infusions (85.8%) were administered through 2 infusion sites using 12mm to 14mm needles.
The analysis of the primary endpoint demonstrated a statistically significant difference between the relapse rates in the HYQVIA group (N=57, 14.0%) compared to the placebo group (N=65, 32.3%) (p=0.0314). The treatment difference of –18.3% (two-sided 95% CI: -32.1%, -3.1%) indicated that HYQVIA demonstrated superiority over placebo in preventing relapse of CIDP.
Kaplan-Meier curves (Figure 2) demonstrated early separation between HYQVIA and placebo at approximately Week 4.
 |
The effect of HYQVIA on activities of daily living was measured by the Rasch-built Overall Disability Scale (R-ODS) centile score. The least squares (LS) mean changes were -1.2 in the HYQVIA group and -6.3 in the placebo group. The LS mean treatment difference between HYQVIA and placebo was 5.1.
Study 2:
A Phase 3b, single-arm, open-label, multicenter, extension study to assess the long-term safety, tolerability, and immunogenicity of HYQVIA for maintenance therapy for CIDP. The study was open to patients who completed Study 1 without CIDP worsening or relapse. The dosing range was 0.4 g/kg to 2.4 g/kg, given in a frequency of 2-, 3-, or 4-week intervals. At the final analysis, the data included 85 patients with a range of follow-ups from 0 to 6.4 years and a total follow-up of 220 patient-years. A total of 3,487 HYQVIA infusions were administered.
The proportion of patients who developed CIDP relapse was 14.3% (10/70) during the study period. The 6-month relapse rate was 2.5%.
How Supplied
HYQVIA is supplied in a dual vial unit of two single dose vials containing the labeled amount of functionally active Immune Globulin Infusion (Human), 10% and rHuPH20. The packaging of this product is not made with natural rubber latex.
The following presentations of HYQVIA are available:
| Immune Globulin Infusion (Human), 10% | rHuPH20 | |||
|---|---|---|---|---|
| NDC Number | Volume | Grams Protein | Volume | Units |
| 0944-2510-02 | 25 mL | 2.5 | 1.25 mL | 200 |
| 0944-2511-02 | 50 mL | 5.0 | 2.5 mL | 400 |
| 0944-2512-02 | 100 mL | 10.0 | 5.0 mL | 800 |
| 0944-2513-02 | 200 mL | 20.0 | 10.0 mL | 1600 |
| 0944-2514-02 | 300 mL | 30.0 | 15.0 mL | 2400 |
Storage and Handling
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Inform patients to immediately report the following signs and symptoms to their healthcare professional:
Self-administration – If self-administration is deemed appropriate by the physician, give clear instructions and training on how to administer HYQVIA. Document their ability to independently administer HYQVIA.
Takeda Pharmaceuticals U.S.A., Inc.
Cambridge, MA 02142
U.S. License No. 1898
HYQVIA is a registered trademark of Baxalta Incorporated.
Takeda and 
©2026 Takeda Pharmaceutical Company Limited. All rights reserved.
Patented: see www.takeda.com/en-us/patents
HYQ353
Patient Information |
The following summarizes important information about HYQVIA (pronounced Hi-Q-via). Please read it carefully before using this medicine. This information does not take the place of talking with your healthcare professional, and it does not include all of the important information about HYQVIA. If you have any questions after reading this, ask your healthcare professional.
What is the most important information that I should know about HYQVIA?
What should I tell my healthcare professional before I start using HYQVIA?
Before starting HYQVIA, tell your healthcare professional if you:
What is HYQVIA?
HYQVIA is a liquid medicine containing immune globulin and Recombinant Human Hyaluronidase. HYQVIA contains IgG antibodies, collected from human plasma donated by healthy people.
Who should not take HYQVIA?
How should I take HYQVIA?
What are the possible or reasonably likely side effects of HYQVIA?
After HYQVIA infusion a temporary, soft swelling may occur around the infusion site, which may last 1 to 3 days, due to the volume of fluid infused.
The following local reactions may occur at the site of infusion and generally go away in a few hours. Local reactions are less likely after the first few infusions.
|
|
The most common side effects of HYQVIA are:
|
|
Antibodies to the hyaluronidase component of HYQVIA were formed in some patients taking HYQVIA. It is not known if there is any long-term effect. In theory, these antibodies could react with your body’s own PH20. PH20 is present in the male reproductive tract. So far, these antibodies have not been associated with increased or new side-effects.
Call your healthcare professional or go to your emergency department right away if you get:
These are not all of the possible side effects for HYQVIA. You can ask your healthcare professional for information that is provided to healthcare professionals. Talk to your healthcare professional about any side effects that bother you or that don’t go away.
How do I store HYQVIA?
Store HYQVIA refrigerated or at room temperature.
Check the expiration date on the carton and vial label. Do not use HYQVIA after the expiration date.
Do not freeze.
Protect from light. You can use the original HYQVIA containers to protect it from light.
Resources at Takeda Available to the Patients
For more information on patient resources and education, please visit www.immunedisease.com.
Do not use HYQVIA at home until you get instructions and training from your healthcare professional.
There are two ways to administer HYQVIA. Refer to the appropriate Instructions For Use (IFU). Your healthcare professional will decide which administration system is right for you. You will take the hyaluronidase first. Then, within 10 minutes, you will take the immune globulin through an infusion pump.
Prepare HYQVIA vial(s):
To administer HYQVIA using Vial Access Devices (VAD)
Refer to the Instructions For Use (IFU) provided with the Vial Access Devices. VAD can be used to administer HYQVIA in adult patients only.
To administer HYQVIA using a needle or needle-less transfer device
Refer to the instructions below.
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Within 10 minutes of completing the infusion of the HY, start the pump to administer the IG.
| |
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|
Takeda Pharmaceuticals U.S.A., Inc.
Cambridge, MA 02142
U.S. License No. 1898
HYQVIA is a registered trademark of Baxalta Incorporated.
Takeda and
©2026 Takeda Pharmaceutical Company Limited. All rights reserved.
Patented: see www.takeda.com/en-us/patents
Revised Date: 6/2026
HYQ353
Immune Globulin Infusion (Human), 10%
Component of HYQVIA®
Single-Dose Vial
Rx Only
Takeda Pharmaceuticals U.S.A., Inc.
Cambridge, MA 02142
U.S. License No. 1898
Infuse 2nd
2.5 g/
25 mL
IG
LE-07-64433
Takeda
Recombinant Human Hyaluronidase
Component of HYQVIA®
Single-Dose Vial
Rx Only
Takeda Pharmaceuticals U.S.A., Inc.
Cambridge, MA 02142
Infuse 1st
HY
1.25 mL
160 units per mL
Takeda
NDC 0944-2510-02
Immune Globulin Infusion (Human), 10%
with Recombinant Human Hyaluronidase
HYQVIA®
For Subcutaneous Administration Only.
Single-dose dual vial unit
Directions for use:
Read the enclosed Package Insert.
No preservative
Rx Only
2.5 g/
25 mL
Takeda
Immune Globulin Infusion (Human), 10%
Component of HYQVIA®
Single-Dose Vial
Rx Only
Takeda Pharmaceuticals U.S.A., Inc.
Cambridge, MA 02142
U.S. License No. 1898
Infuse 2nd
5 g/
50 mL
IG
LE-07-64435
Takeda
Recombinant Human Hyaluronidase
Component of HYQVIA®
Single-Dose Vial
Rx Only
Takeda Pharmaceuticals U.S.A., Inc.
Cambridge, MA 02142
Infuse 1st
HY
2.5 mL
160 units per mL
Takeda
NDC 0944-2511-02
Immune Globulin Infusion (Human), 10%
with Recombinant Human Hyaluronidase
HYQVIA®
For Subcutaneous Administration Only.
Single-dose dual vial unit
Directions for use:
Read the enclosed Package Insert.
No preservative
Rx Only
5 g/
50 mL
Takeda
Immune Globulin Infusion (Human), 10%
Component of HYQVIA®
Single-Dose Vial
Rx Only
Takeda Pharmaceuticals U.S.A., Inc.
Cambridge, MA 02142
U.S. License No. 1898
Infuse 2nd
10 g/
100 mL
IG
LE-07-64437
Takeda
Recombinant Human Hyaluronidase
Component of HYQVIA®
Single-Dose Vial
Rx Only
Takeda Pharmaceuticals U.S.A., Inc.
Cambridge, MA 02142
Infuse 1st
5 mL
160 units per mL
HY
Takeda
NDC 0944-2512-02
Immune Globulin Infusion (Human), 10%
with Recombinant Human Hyaluronidase
HYQVIA®
For Subcutaneous Administration Only.
Single-dose dual vial unit
Directions for use:
Read the enclosed Package Insert.
No preservative
Rx Only
10 g/
100 mL
Takeda
Immune Globulin Infusion (Human), 10%
Component of HYQVIA®
Single-Dose Vial
Rx Only
Takeda Pharmaceuticals U.S.A., Inc.
Cambridge, MA 02142
U.S. License No. 1898
Infuse 2nd
20 g/
200 mL
IG
LE-07-64439
Takeda
Recombinant Human Hyaluronidase
Component of HYQVIA®
Single-Dose Vial
Rx Only
Takeda Pharmaceuticals U.S.A., Inc.
Cambridge, MA 02142
Infuse 1st
HY
10 mL
160 units per mL
LE-07-62670
Takeda
NDC 0944-2513-02
Immune Globulin Infusion (Human), 10%
with Recombinant Human Hyaluronidase
HYQVIA®
For Subcutaneous Administration Only.
Single-dose dual vial unit
Directions for use: Read the enclosed Package Insert.
No preservative
Rx Only
20 g/
200 mL
Takeda
Immune Globulin Infusion (Human), 10%
Component of HYQVIA®
Single-Dose Vial
Rx Only
Takeda Pharmaceuticals U.S.A., Inc.
Cambridge, MA 02142
U.S. License No. 1898
Infuse 2nd
30 g/
300 mL
IG
LE-07-64441
Takeda
Recombinant Human Hyaluronidase
Component of HYQVIA®
Single-Dose Vial
Rx Only
Takeda Pharmaceuticals U.S.A., Inc.
Cambridge, MA 02142
Infuse 1st
HY
15 mL
160 units per mL
LE-07-62673
Takeda
NDC 0944-2514-02
Immune Globulin Infusion (Human), 10%
with Recombinant Human Hyaluronidase
HYQVIA®
For Subcutaneous Administration Only.
Single-dose dual vial unit
Directions for use: Read the enclosed Package Insert.
No preservative
Rx Only
30 g/
300 mL
Takeda
| Resource | Code type | Value | Equivalent identifiers | Source image |
|---|---|---|---|---|
| Barcode | DataBar Stacked | (01)00309442715252 | GTIN-14: 00309442715252 GTIN-12: 309442715252 UPC-A: 309442715252 EAN-13: 0309442715252 GTIN storage (14 digits): 00309442715252 | hyqvia-21.jpg |
| Barcode | DataBar Stacked | (01)00309442716051 | GTIN-14: 00309442716051 GTIN-12: 309442716051 UPC-A: 309442716051 EAN-13: 0309442716051 GTIN storage (14 digits): 00309442716051 | hyqvia-24.jpg |
| Barcode | DataBar Stacked | (01)00309442717102 | GTIN-14: 00309442717102 GTIN-12: 309442717102 UPC-A: 309442717102 EAN-13: 0309442717102 GTIN storage (14 digits): 00309442717102 | hyqvia-27.jpg |
| Barcode | DataBar Stacked | (01)00309442720034 | GTIN-14: 00309442720034 GTIN-12: 309442720034 UPC-A: 309442720034 EAN-13: 0309442720034 GTIN storage (14 digits): 00309442720034 | hyqvia-22.jpg |
| Barcode | DataBar Stacked | (01)00309442723035 | GTIN-14: 00309442723035 GTIN-12: 309442723035 UPC-A: 309442723035 EAN-13: 0309442723035 GTIN storage (14 digits): 00309442723035 | hyqvia-31.jpg |
| Barcode | DataBar Stacked | (01)00309442724032 | GTIN-14: 00309442724032 GTIN-12: 309442724032 UPC-A: 309442724032 EAN-13: 0309442724032 GTIN storage (14 digits): 00309442724032 | hyqvia-34.jpg |
| Data code | Data Matrix | 0764901 | hyqvia-23.jpg | |
| Data code | Data Matrix | 0764902 | hyqvia-26.jpg | |
| Data code | Data Matrix | 0764903 | hyqvia-29.jpg |
| Package NDC | Billing unit | Product NDC | DailyMed indexing SPL | SPL version | Effective |
|---|---|---|---|---|---|
| 0944-2510-02 | ML - Milliliter | 0944-2510 | 325c56e6-e6e9-498f-9ca8-3341da1dabf6 | 1 | 2014-10-03 |
| 0944-2511-02 | ML - Milliliter | 0944-2511 | a4f5ea5b-1649-4d4d-a02b-ae4336707c46 | 1 | 2014-10-03 |
| 0944-2512-02 | ML - Milliliter | 0944-2512 | a52eb946-13e8-430a-9de7-34269783b490 | 1 | 2014-10-03 |
| 0944-2513-02 | ML - Milliliter | 0944-2513 | 0d8620e6-22a1-49f1-8d89-1fbf7fafbe13 | 1 | 2014-10-03 |
| 0944-2514-02 | ML - Milliliter | 0944-2514 | f66d898b-1f51-4003-95ae-8108b1012873 | 1 | 2014-10-03 |
| Ingredient | Type | UNII | SPL version | Uploaded |
|---|---|---|---|---|
| HUMAN IMMUNOGLOBULIN G | ACTIVE INGREDIENT | 66Y330CJHS | 1 | |
| HYALURONIDASE (HUMAN RECOMBINANT) | ACTIVE INGREDIENT | 743QUY4VD8 | 1 | |
| HUMAN IMMUNOGLOBULIN G | ACTIVE MOIETY | 66Y330CJHS | 1 | |
| HYALURONIDASE (HUMAN RECOMBINANT) | ACTIVE MOIETY | 743QUY4VD8 | 1 | |
| ALBUMIN HUMAN | INACTIVE INGREDIENT | ZIF514RVZR | 1 | |
| CALCIUM CHLORIDE | INACTIVE INGREDIENT | M4I0D6VV5M | 1 | |
| EDETATE DISODIUM | INACTIVE INGREDIENT | 7FLD91C86K | 1 | |
| GLYCINE | INACTIVE INGREDIENT | TE7660XO1C | 1 | |
| SODIUM CHLORIDE | INACTIVE INGREDIENT | 451W47IQ8X | 1 | |
| SODIUM HYDROXIDE | INACTIVE INGREDIENT | 55X04QC32I | 1 | |
| SODIUM PHOSPHATE | INACTIVE INGREDIENT | SE337SVY37 | 1 |
Every source-derived product name is available through these pages.
| BLA | Proprietary name | Proper name | License type | Status | Latest source |
|---|---|---|---|---|---|
| 125402 | Hyqvia | Immune Globulin Infusion (Human), 10% with Recombinant Human Hyaluronidase | 351(a) | Rx | 2026-09-01 |
Every source-derived ingredient row is available through these pages.
| Version | Effective date | Source | Hydrated |
|---|---|---|---|
| 22 | 2026-02-04 | full-release | 2026-06-01 02:52:26 |
| 21 | 2025-11-25 | monthly-update | 2026-06-03 17:47:06 |
Inactive Ingredient Database values describe FDA-listed use contexts. The match method and ambiguity count are shown because ingredient names, routes, and dosage forms are not always unique. Browse recovered IID releases and source provenance.
| DailyMed ingredient | IID ingredient | UNII | Dosage form / route | Potency | Maximum daily exposure | Match |
|---|---|---|---|---|---|---|
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | SOAP / TOPICAL | 1.26 %w/w | ||
| EDETATE DISODIUM | EDETATE DISODIUM | 7FLD91C86K | SPRAY / NASAL | 1 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION / RETROBULBAR | 648 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | SUSPENSION, EXTENDED RELEASE / INTRADERMAL | ADJ PH | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INHALANT / RESPIRATORY (INHALATION) | 3 mg | ||
| EDETATE DISODIUM | EDETATE DISODIUM | 7FLD91C86K | SYSTEM / TOPICAL | 126 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION / SOFT TISSUE | ADJ PH | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRATHECAL | ADJ PH | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, POWDER, FOR SOLUTION / SUBCUTANEOUS | 0.68 %w/v | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | SOLUTION / URETERAL | ADJ PH | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / INTRA-ARTICULAR | ADJ PH | ||
| GLYCINE | GLYCINE | TE7660XO1C | POWDER / RESPIRATORY (INHALATION) | 2 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | SOLUTION / NASAL | 330 mg | ||
| EDETATE DISODIUM | EDETATE DISODIUM | 7FLD91C86K | CONCENTRATE / ORAL | 20 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SUSPENSION / INTRALESIONAL | ADJ PH | ||
| EDETATE DISODIUM | EDETATE DISODIUM | 7FLD91C86K | INJECTION, POWDER, FOR SUSPENSION / INTRAVENOUS | 0.4 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION / PARENTERAL | ADJ PH | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION / INTRACAUDAL | 210 mg | ||
| SODIUM PHOSPHATE | SODIUM PHOSPHATE | SE337SVY37 | INJECTION / SUBCUTANEOUS | 0.38 %w/v | ||
| EDETATE DISODIUM | EDETATE DISODIUM | 7FLD91C86K | INJECTION, EMULSION / INTRAVENOUS | 59 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SUSPENSION / SOFT TISSUE | 26 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, POWDER, FOR SUSPENSION / INTRAVENOUS | ADJ PH | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, POWDER, FOR SOLUTION / INTRATHECAL | 1.35 mg | ||
| EDETATE DISODIUM | EDETATE DISODIUM | 7FLD91C86K | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 19 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SUSPENSION / INTRASYNOVIAL | ADJ PH | ||
| EDETATE DISODIUM | EDETATE DISODIUM | 7FLD91C86K | SOLUTION / AURICULAR (OTIC) | 0.1 %w/v | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | TABLET, EXTENDED RELEASE / ORAL | 13 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | SWAB / TOPICAL | 0.01 %w/w | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | SUSPENSION / OPHTHALMIC | ADJ PH | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | GRANULE, FOR SUSPENSION / ORAL | ADJ PH | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | LIQUID / INTRAVENOUS | 6320 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / INFILTRATION | ADJ PH | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION / SUBCUTANEOUS | 1486 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | CREAM, AUGMENTED / TOPICAL | 6 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | SUSPENSION/ DROPS / AURICULAR (OTIC) | ADJ PH | ||
| SODIUM PHOSPHATE | SODIUM PHOSPHATE | SE337SVY37 | INJECTION / INTRAMUSCULAR | 10.6 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | ELIXIR / ORAL | ADJ PH | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | POWDER, FOR SUSPENSION / ORAL | 98 mg | ||
| EDETATE DISODIUM | EDETATE DISODIUM | 7FLD91C86K | TABLET, EFFERVESCENT / ORAL | 32 mg | ||
| GLYCINE | GLYCINE | TE7660XO1C | TABLET, ORALLY DISINTEGRATING / ORAL | 60 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | LIQUID / TOPICAL | ADJ PH | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAVENOUS | 2916 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | LIQUID / NASAL | 7.4 mg/1ml | ||
| EDETATE DISODIUM | EDETATE DISODIUM | 7FLD91C86K | SUSPENSION / RESPIRATORY (INHALATION) | 0.01 %w/v | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, POWDER, FOR SOLUTION / INTRAMUSCULAR | 7.01 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | ENEMA / RECTAL | 0.44 %v/v | ||
| EDETATE DISODIUM | EDETATE DISODIUM | 7FLD91C86K | TABLET / ORAL | 100 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | SOLUTION/ DROPS / AURICULAR (OTIC) | 18 mg | ||
| EDETATE DISODIUM | EDETATE DISODIUM | 7FLD91C86K | INJECTION, SUSPENSION / INTRA-ARTICULAR | 1 mg | ||
| EDETATE DISODIUM | EDETATE DISODIUM | 7FLD91C86K | INJECTION / SOFT TISSUE | 0.05 %w/v | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, POWDER, FOR SOLUTION / INTRAPLEURAL | 226 mg | ||
| SODIUM PHOSPHATE | SODIUM PHOSPHATE | SE337SVY37 | SOLUTION / ORAL | 27 mg/5ml | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | TABLET, ORALLY DISINTEGRATING / ORAL | 10 mg | ||
| EDETATE DISODIUM | EDETATE DISODIUM | 7FLD91C86K | DROPS / OPHTHALMIC | 0.05 %w/v | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | POWDER, FOR SUSPENSION / ENDOTRACHEAL | 46.76 mg | ||
| GLYCINE | GLYCINE | TE7660XO1C | TABLET / ORAL | 163.31 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION / INTRA-ARTICULAR | ADJ PH | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | TABLET, DELAYED RELEASE / ORAL | 97 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | GEL, METERED / TRANSDERMAL | 350 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | SYSTEM / TOPICAL | 3.1 mg |
OpenFDA label data provides additional search and identifier links. DailyMed’s Structured Product Label is the canonical label on FDA.report. Matching records are deduplicated before they are shown below.
| Brand | Generic | Manufacturer | SPL set ID | Effective date | Available safety fields | Join |
|---|---|---|---|---|---|---|
| ASCENIV | HUMAN IMMUNOGLOBULIN G | ADMA Biologics, Inc. | d74f4360-3b51-496c-96fb-84c3976958d2 | 2026-04-30 | Boxed warning, Warnings, Adverse reactions | HUMAN IMMUNOGLOBULIN G |
| QIVIGY kthm | HUMAN IMMUNOGLOBULIN G | Kedrion S.p.A. | 6f1933e0-240f-48f4-b246-8a30e63a4160 | 2026-02-02 | Boxed warning, Warnings, Adverse reactions | HUMAN IMMUNOGLOBULIN G |
Adverse event summaries are temporarily unavailable. Other product information remains available.
