Introduction
Xembify (immune globulin subcutaneous, human - klhw) is a sterile, preservative-free solution of human immunoglobulin G (IgG) for subcutaneous administration. It is indicated for the treatment of primary humoral immunodeficiency (PI) in adult and pediatric patients 2 years of age and older. Xembify is part of the immunoglobulin replacement therapy class, providing broad-spectrum antibody protection against bacterial and viral pathogens.
Mechanism of Action
Xembify contains IgG antibodies that provide passive immunity by neutralizing toxins, opsonizing pathogens, and activating complement pathways. The drug replaces missing antibodies in patients with primary immunodeficiency disorders, thereby reducing the frequency and severity of infections. The subcutaneous formulation allows for sustained IgG levels through regular administration, maintaining protective serum immunoglobulin concentrations.
Indications
Xembify is FDA-approved for:
- Treatment of primary humoral immunodeficiency in adults and pediatric patients 2 years of age and older
- This includes conditions such as X-linked agammaglobulinemia, common variable immunodeficiency, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies
Dosage and Administration
Initial Dose:- Calculate based on previous intravenous or subcutaneous IgG therapy
- For patients switching from IVIG: administer first dose 1 week after last IVIG infusion
- Initial weekly dose (grams) = previous IVIG dose (grams) × 1.37
- Divide by number of weeks between IVIG doses
- Weekly dosage range: 100-200 mg/kg body weight
- Individualize dose based on clinical response and serum IgG trough levels
- Maximum infusion rate: 60 mL/hr per site (adults); 25 mL/hr per site (children 2-5 years)
- Maximum volume per site: 25 mL (adults); 10 mL (children 2-5 years)
- Administer subcutaneously using an infusion pump
- Multiple infusion sites may be used simultaneously (typically 2-8 sites)
- Preferred sites: abdomen, thighs, upper arms, and/or lateral hip/buttocks
- Rotate infusion sites with each administration
- Renal impairment: Use with caution
- Hepatic impairment: No specific recommendations
- Geriatric patients: Individualize based on comorbidities
- Pediatric patients: Safety established down to 2 years of age
Pharmacokinetics
Absorption:- Bioavailability: Complete following subcutaneous administration
- Time to peak concentration: Approximately 3-5 days post-infusion
- Distributed throughout extracellular fluid
- Volume of distribution: Approximately 0.1 L/kg
- IgG is metabolized through proteolytic degradation
- Half-life: Approximately 30-40 days
- Primarily through catabolism in reticuloendothelial system
- Small amounts may be eliminated in urine
Contraindications
- History of anaphylactic or severe systemic reaction to human immune globulin
- Selective IgA deficiency with known antibodies against IgA
- Hypersensitivity to any component of the formulation
Warnings and Precautions
Thrombotic Events: IG products have been associated with thrombotic events. Use with caution in patients with risk factors for thrombosis. Renal Dysfunction: May cause renal dysfunction, acute renal failure, osmotic nephrosis, and death. Use caution in patients with renal impairment. Aseptic Meningitis Syndrome: May occur, especially with high doses or rapid infusion. Hemolysis: IG products can contain blood group antibodies that may cause hemolytic anemia. Transmissible Infectious Agents: Although screened and treated, may potentially transmit infectious agents. Hyperproteinemia: May occur, affecting laboratory determinations. Inflammatory Conditions: Monitor for signs of inflammation at infusion sites.Drug Interactions
Live Virus Vaccines: May diminish the immune response to live virus vaccines. Defer vaccination for 3 months after Xembify administration. Other Immunoglobulin Products: Do not administer concurrently with other IgG products. Blood Products: Potential interference with serological testing and red blood cell cross-matching.Adverse Effects
Most Common Adverse Reactions (≥5% of patients):- Local reactions: swelling, redness, itching, pain at infusion site
- Headache
- Fatigue
- Nausea
- Diarrhea
- Fever
- Vomiting
- Abdominal pain
- Thrombotic events
- Renal dysfunction/failure
- Aseptic meningitis syndrome
- Severe hypersensitivity reactions
- Hemolytic anemia
- Transfusion-related acute lung injury (TRALI)
Monitoring Parameters
Before Therapy:- Serum IgG trough levels
- Renal function tests (BUN, creatinine)
- Complete blood count with differential
- Blood type and antibody screen if high risk for hemolysis
- Serum IgG trough levels (every 3-6 months once stable)
- Renal function monitoring
- Signs and symptoms of thrombosis
- Local infusion site reactions
- Vital signs during initial infusions
- Signs of aseptic meningitis (headache, fever, nausea)
- Hemoglobin/hematocrit if signs of hemolysis appear
- Annual comprehensive metabolic panel
- Annual thyroid function tests
- Quality of life assessment
- Infection frequency and severity
Patient Education
Administration Instructions:- Proper technique for subcutaneous infusion
- Site rotation and care
- Recognition of proper vs. improper infusion sites
- Pump operation and troubleshooting
- Signs of local reactions and management strategies
- Symptoms requiring immediate medical attention:
- Severe headache with nausea/vomiting - Chest pain or shortness of breath - Decreased urine output - Yellowing of skin or eyes - Severe abdominal pain
Lifestyle Considerations:- Importance of regular infusions
- Travel considerations
- Infection prevention strategies
- When to contact healthcare provider
- Proper storage conditions (2-8°C)
- Do not freeze
- Protection from light
- Proper disposal of supplies
References
1. Xembify [package insert]. Grifols Therapeutics LLC; 2021. 2. Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136(5):1186-1205. 3. Orange JS, Grossman WJ, Navickis RJ, et al. Impact of trough IgG on pneumonia incidence in primary immunodeficiency: A meta-analysis of clinical studies. Clin Immunol. 2010;137(1):21-30. 4. Perez EE, Orange JS, Bonilla F, et al. Update on the use of immunoglobulin in human disease: A review of evidence. J Allergy Clin Immunol. 2017;139(3S):S1-S46. 5. FDA Approval Letter: Xembify. US Food and Drug Administration; 2019. 6. Clinical trial data: NCT03310125, NCT03310207