immune globulin SC (Hizentra, HyQvia, Cuvitru, Gammagard Liquid SC, Gamunex-C SC)

Dosing and uses of Hizentra, HyQvia (immune globulin SC)

• Adult
• Pediatric

 

Adult dosage forms and strengths

subcutaneous injectable solution

• 10% (100mg/mL) (Gamunex-C, Gammagard Liquid)
• 10% (100mg/mL) duovial set with recombinant human hyaluronidase 160 units/mL (HyQvia)
• 20% (200mg/mL) (Hizentra)

 

Primary Immune Deficiency

Indicated for primary immunodeficiency; this includes, but is not limited to, common variable immunodeficiency (CVID), X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies

Individualize the dose based on the patient’s clinical response and serum IgG trough levels; obtain baseline serum IgG trough level to guide subsequent dosage adjustments

Before initiating, ensure that patients have received IGIV treatment at regular intervals for at least 3 months

Initiate weekly dosing 1 week after patient’s last IGIV dose

Hizentra

• May be administered as a SC infusion at regular intervals as daily up to biweekly (ie, q2Weeks)

Gamunex-C

• Administered as weekly SC infusion
• Initial SC dose: 1.37 x current IVIG dose in mg/kg divided by number of weeks between IV doses
• Not to exceed 20 mL/hr/infusion site

Gammagard Liquid

• Administered as weekly SC infusion
• Initial SC dose: Initial SC dose: 1.37 x current IVIG dose in mg/kg divided by number of weeks between IV doses
• ≥40 kg: Not to exceed 30 mL/infusion site at rate of 20 mL/hr/site; for maintenance dose, may increase to 30 mL/hr site
• <40 kg: Not to exceed 20 mL/infusion site at rate of 15 mL/hr site; for maintenance dose, may increase to 20 mL/hr site

HyQvia

• Initiating
  • For patients previously on another IgG treatment, administer the first dose approximately 1 week after the last infusion of their previous treatment
  • Increase the dose and frequency from a 1-week dose to a 3- or 4-week dose (see titration schedule)
  • Initiating treatment at a full monthly dose was not evaluated in clinical trials
• Titration schedule
  • Titrate to dosage interval of every 3-4 weeks
  • Week 1: 1st infusion (weekly dose) at 25% of targeted dose
  • Week 2: 2nd infusion (q2week dose) at 50% of targeted dose
  • Week 3: No infusion
  • Week 4: 3rd infusion (q3week dose) at 75% of targeted dose
  • Week 5: No infusion
  • Week 6: No infusion
  • Week 7: 4th infusion (q4week dose) at 100% of targeted dose (if required)
• Switching from IVIG
  • Administer HyQvia at the same dose and frequency as the previous IV treatment, after the initial dose titration
• Patients naïve to IgG treatment or switching from immune globulin human SC
  • 300-600 mg/kg SC at 3 to 4 week intervals, after initial titration

Cuvitru

• Can be administered at regular intervals from daily up to q2weeks
• Initiating
  • Individualize the dose based on the patient’s pharmacokinetic and clinical response
  • Monitor serum IgG trough levels regularly to guide subsequent dose adjustments and dosing intervals as needed
• Switching from IVIG or adults switching from HyQvia
  • Begin Cuvitru 1 week after the patient’s last IGIV or HyQvia infusion
  • Establish the initial weekly dose by converting the monthly IGIV or HyQvia dose into an equivalent weekly dose and increasing it using a dose adjustment factor
  • To calculate the initial weekly dose, divide the previous IGIV or HyQvia dose in grams by the number of weeks between IV doses; then multiply this dose by the dose adjustment factor of 1.3
• Switching from another immune globulin human SC
  • Cuvitru weekly dose (in grams) is recommended to be the same as the weekly dose of prior IGSC treatment (in grams)
  • Doses divided over the course of a week, once weekly, or biweekly, achieve similar exposure when administered regularly at steady-state

 

Dosing Considerations

Adjust dose by measuring serum trough IgG trough levels and calculating difference from baseline IVIG trough levels, then refer to dosage adjustment tables listed within prescribing information for particular product

 

Demyelinating Polyneuropathy (Orphan)

Hizentra 20%: Orphan designation for treatment of chronic inflammatory demyelinating polyneuropathy (CIDP)

Sponsor

• CSL Behring; 1020 First Avenue, P. O. Box 61501; King of Prussia, PA 19406

 

Pediatric dosage forms and strengths

subcutaneous injectable solution

• 10% (100mg/mL) (Gamunex-C, Gammagard Liquid)
• 20% (200mg/mL) (Hizentra, Cuvitru)

 

Primary Immune Deficiency

<2 years: Safety and efficacy not established

Individualize the dose based on the patient’s clinical response and serum IgG trough levels; obtain baseline serum IgG trough level to guide subsequent dosage adjustments

Before initiating, ensure that patients have received IGIV treatment at regular intervals for at least 3 months

Initiate weekly dosing 1 week after patient’s last IGIV dose

Hizentra

• May be administered as weekly or biweekly (ie, q2Weeks) SC infusion
• Initial SC weekly dose: 1.53 x current IVIG dose in mg/kg divided by number of weeks between IV doses
• Initial SC biweekly dose: For biweekly dosing, start treatment 1 or 2 weeks after the last IGIV infusion or 1 week after that last weekly Hizentra infusion
• SC infusion volume: Not to exceed 15 mL/infusion site; for maintenance dose, may increase to 20 mL/site after 4th infusion, and then 25 mL/site as tolerated
• SC infusion rate: Not to exceed 15 mL/hr/site for 1st dose; may increase to 25 mL/hr/site for subsequent infusions

Cuvitru

• Can be administered at regular intervals from daily up to q2weeks
• Initiating
  • Individualize the dose based on the patient’s pharmacokinetic and clinical response
  • Monitor serum IgG trough levels regularly to guide subsequent dose adjustments and dosing intervals as needed
• Switching from IVIG or adults switching from HyQvia
  • Begin Cuvitru 1 week after the patient’s last IGIV or HyQvia infusion
  • Establish the initial weekly dose by converting the monthly IGIV or HyQvia dose into an equivalent weekly dose and increasing it using a dose adjustment factor
  • To calculate the initial weekly dose, divide the previous IGIV or HyQvia dose in grams by the number of weeks between IV doses; then multiply this dose by the dose adjustment factor of 1.3
• Switching from another immune globulin human SC
  • Cuvitru weekly dose (in grams) is recommended to be the same as the weekly dose of prior IGSC treatment (in grams)
  • Doses divided over the course of a week, once weekly, or biweekly, achieve similar exposure when administered regularly at steady-state

Gamunex-C

• Administered as weekly SC infusion
• Initial SC dose: 1.37 x current IVIG dose in mg/kg divided by number of weeks between IV doses
• Not to exceed 20 mL/hr/infusion site

Gammagard Liquid

• Administered as weekly SC infusion
• Initial SC dose: Initial SC dose: 1.37 x current IVIG dose in mg/kg divided by number of weeks between IV doses
• ≥40 kg: Not to exceed 30 mL/infusion site at rate of 20 mL/hr/site; for maintenance dose, may increase to 30 mL/hr site
• <40 kg: Not to exceed 20 mL/infusion site at rate of 15 mL/hr site; for maintenance dose, may increase to 20 mL/hr site

 

Dosing Considerations

Adjust dose by measuring serum trough IgG trough levels and calculating difference from baseline IVIG trough levels, then refer to dosage adjustment tables listed within prescribing information for particular product

 

Hizentra, HyQvia (immune globulin SC) adverse (side) effects

>10%

Injection site reactions (92-100%)

Headache (26.5-48%)

GI disorder (37%)

Fever (25%)

Sore throat (8.2-17%)

Rash (10.2-17%)

Cough (16.3%)

Diarrhea (10-14.3%)

Fatigue (12.2%)

Allergic reaction (11%)

Abdominal pain (10.2%)

Pain (8.2-10%)

 

1-10%

Arthralgia (8.2%)

Migraine (8.2%)

Epistaxis (8.2%)

Nausea (4.1%)

Rash (4.1%)

 

Warnings

Black box warnings

Thrombosis

• Thrombosis may occur with immune globulin products
• Risk factors include advanced age, prolonged immobilization, hypercoagulable conditions, history of thrombosis, estrogen use, indwelling central vascular catheters, hyperviscosity, and CV risk factors
• For at risk patients, use lowest possible dose and infusion rate, ensure adequate hydration before administration, assess blood viscosity, and monitor for signs and symptoms of thrombosis

 

Contraindications

Hypersensitivity to immune globulins or solution components

Selected IgA deficiency with known antibody against IgA

Severe thrombocytopenia or coagulation disorders

Hyperprolinemia (Hizentra contains the stabilizer L-proline)

 

Cautions

Initial treatment should be done in clinical setting (due to possibility of anaphylactic reactions)

May transiently impair efficacy of live attenuated viruses

Passive transmission of antibodies may yield false positive serological tests (eg, Coombs)

Products made from human plasma can contain infectious agents (eg, viruses and, theoretically, Creutzfeldt-Jakob disease [CJD])

Subcutaneous administration associated with increased risk of hematoma

Hemolytic anemia reported (monitor)

Renal dysfunction or renal failure has been associated with IG therapy; monitor renal function and urine output

Hyperproteinemia and hyponatremia may occur

Aseptic meningitis syndrome reported

Not for IV

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Excretion in milk unknown; use with caution

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Hizentra, HyQvia (immune globulin SC)

Mechanism of action

Pooled human immune globulins from donors used as replacement therapy for primary and secondary immunodeficiencies, and IgG antibodies against viral, bacteria, parasitic, and mycoplasma antigens; provides passive immunity through an increase in atibody titer and antigen-antibody reaction potentiaL

 

Pharmacokinetics

Peak plasma levels: 1090-2825 mg/dL for doses 141-381 mg/kg

Bioavailability: 73%

Peak plasma time: 2.9 days

 

Administration

SC Administration

For multiple site infusion, divide sites at least 2 inches apart

For weekly dosing, use up to 4 sites simultaneously or 12 sites consecutively per infusion

Infusion sites include abdomen, thighs, upper arm, lateral hip; rotate injection sites every week

Hizentra

• Initial SC weekly dose: 1.37 x previous IVIG dose (in grams)divided by number of weeks between IVIG doses
• Initial SC biweekly dose: For biweekly dosing, start treatment 1 or 2 weeks after the last IGIV infusion or 1 week after that last weekly Hizentra infusion; administer twice the calculated weekly dose
• Frequent dosing (2 to 7 times per week): Divide the calculated weekly dose by the desired number of times per week
• Individualize the dose based on patient’s clinical response to therapy (IgG trough level); refer to the prescribing information dose adjustment table for further detail
• SC infusion volume: Not to exceed 15 mL/infusion site for 1st dose; for maintenance dose, may increase to 20 mL/site after 5th infusion, and then 25 mL/site as tolerated
• SC infusion rate: Not to exceed 15 mL/hr/site for 1st dose; may increase to 25 mL/hr/site for subsequent infusions

HyQvia

• Administer by a healthcare professional, caregiver or self-administered by the patient after appropriate training
• Infusion requires an infusion pump capable of infusion rates up to 300 mL/hr/site; to ensure maximum flow rates, use a SC set that is 24 gauge and labeled for high flow rates
• Infuse the 2 components sequentially, beginning with the recombinant human hyaluronidase
• Initiate the infusion of the full dose of the IG 10% through the same SC needle set within ~10 minutes of the hyaluronidase infusion
• For each full or partial vial of IG 10% used, administer the entire contents of the hyaluronidase vial
• Infusion site(s): Infuse in abdomen or thighs; if 2 sites are used, give on opposite sides of body and administer half of total volume of hyaluronidase in each site
• Volume per site: Up to 600 mL/site for patients ≥40 kg and up to 300 mL/site for patients <40 kg

Infusion rate (HyQvia)

• Hyaluronidase: 1-2 mL/min SC (as tolerated)
• Immune globulin, first 2 infusions (<40 kg): 5 mL/hr initially; double infusion rate every 5-15 minutes until 80 mL/hr for remainder of infusion
• Immune globulin, first 2 infusions (≥40 kg): 10 mL/hr initially; after 5-10 minutes increase to 30 mL/min, and then double infusion rate every 5-15 minutes until 240 mL/hr for remainder of infusion
• Immune globulin, subsequent 2-3 infusions (<40 kg): 10 mL/hr initially; after 5-10 minutes increase to 30 mL/min, and then double infusion rate every 5-15 minutes until 240 mL/hr for remainder of infusion
• Immune globulin, subsequent 2-3 infusions (≥40 kg): Beginning with 10 mL/hr, increase every 5-15 minutes to 30 mL/hr, 120 mL/hr, 240 mL/hr, and finally 300 mL/hr for remainder of infusion

Cuvitru

• Infusion site
  • Areas of infusion include abdomen, thighs, upper arms, or lateral hip
  • May be infused into multiple infusion sites
  • Use up to 4 sites simultaneously
  • Infusion sites should be at least 4-inches apart, avoiding bony prominences
  • Rotate sites with each administration
• Volume per site
  • To calculate the number of sites to be used, divide the total volume to be infused by the maximum volume/site (up to 60 mL/site) to be infused
  • Simultaneous SC infusion at multiple sites can be facilitated by use of a multineedle administration set
• Infusion rate
  • First 2 infusions: 10-20 mL/hr/site
  • Subsequent infusions: May increase to 60 mL/hr/site as tolerated
  • If utilizing 4 infusion sites, the maximum infusion rate for all sites combined is 240 mL/hr