Pentaglobin ®
Author: Dr. Wamiq Ansari
Last Updated:
Composition
a. 1 mL of Pentaglobin solution contains 50 mg of Human Plasma Proteins.
b. Out of 50 mg plasma proteins, 95% immunoglobins are present in following composition;
- i. IgM: 6 mg.
- ii. IgA: 6 mg.
- iii. IgG: 38 mg.
c. 38 mg IgG in 1 mL is constituted by subclasses as;
- i. IgG1: 63%.
- ii. IgG2: 26%.
- iii. IgG3: 4%.
- iv. IgG4: 7%.
d. All the protein components are obtained by Plasma of Human Donors.
e. Contains following Excipients (with studied effect);
- i. Glucose: 25 mg.
- ii. Sodium: 1.79 mg (0.078 mmol).
Mechanism of Action
1. Immunoglobulin M (IgM):
Binds to antigen on bacteria and promotes complement activation, leading to clearence of pathogen from bloodstream.
2. Immunoglobulin A:
Prevents adhesion of bacteria to mucosal surfaces, strengthening mucosal immunity.
3. Immunoglobulin G:
Promotes opsonization and phagocytosis of bacteria.
Pharmacokinetics
1. Half Life: Shorter half life of IgM (around 4-5 days) compared to IgG (atleast 21 days).
2. Metabolism: Reticuloendothelial System (Liver and Spleen).
3. Excretion: Very small amount in urine.
Indications
As an adjunctive therapy with broad-spectrum antibiotics in following conditions;
- Neonatal Sepsis (especially Gram negative bacteria)..
- Severe Bacterial Infections in all age groups , not responding to antibiotics.
- Septic Shock with Multi-Organ Failure.
- Immunocompromised state (Corticosteroid therapy for more than 4-6 weeks, known chronic illness or known immunodeficiency disease).
Contraindications
1. IgA deficiency with Anti-IgA antibodies (Risk of Severe Anaphylaxis)..
2. Hypercoagulable states (Risk of Thrombosis).
3. Severe Renal Impairment (Risk of Acute Kidney Injury).
4. Severe Hypersensitivity to Human Immunoglobulin products.
Dosage
Parenteral
| Neonates | 5mL/kg or 0.25gm/kg IV infusion x Once a day. (For 3 consecutive days) |
| Children | a. Severe Bacterial Infection : Same as Neonatal Dose. b. Immunocompromised state : 3-5 mL/kg or 0.15-0.25gm/kg IV Infusion x Once a week. |
Rate of Infusion
Neonates and Infants
First 30 minutes : 1.7 mL/kg/hour.
After 30 minutes (if not adverse effect occurs) : 1.2 to 1.7 mL/kg/hour.
Children
Prefer Method : Same as Neonates and Infants.
Alternate Method :
- If total calculated dose is 100 mL or less : 0.4 mL/kg/hour.
- If total calculated dose is more than 100 mL :
| For First 100 mL | 0.4 mL/kg/hour |
| Remaining Dose | 0.2 mL/kg/hr (must be completed within 48-72 hours). |
Special Precautions
1. Adequate hydration before pentaglobin infusion.
2. Pre- and Post-infusion Serum Creatinine and Blood Urea Nitrogen (BUN).
3. Avoid concomittant use of Loop Diuretics.
4. Must be stored at 2° to 8° (increases Shelf-Life up to 2 years).
5. Must not be diluted in other fluids.
6. Do not give Live-attenuated vaccines for 3 months after pentaglobin infusion.
7. Strictly avoid Measles vaccination for atleast 1 year after pentaglobin infusion.
Renal Adjustment Dosage
| Mild to Moderate Impairment | i. Infusion rate must be less than 0.4 mL/kg/hour. ii. Close Renal monitoring. |
| Severe Impairment | i. Avoid use until benefits outweigh risks. ii. If very necessary, then administer at the lowest possible dose and infusion rate, along with adequate hydration and strict renal monitoring. |
Hepatic Adjustment Dosage
1. No evidence of dose adjustment in hepatic impairment.
2. Hepatic impairment may prolong Immunoglobulin metabolism to mimimal extent.
Adverse Effects
| Most Common | i. Fever, Chills, headache and Vomiting. ii. Hypotension or Hypertension (during infusion). |
| Life Threatening | i. Severe Anaphylaxis. ii. Thromboembolism. iii. Aseptic Meningitis. iv. Hemolysis. v. Acute Kidney Injury. |
References
1. https://paviour.org/human-igm-enriched-immunoglobulin/#:~:text=Infusion%20rate%3A%20in%20neonates%20and,is%20reached%20within%2072%20hours.
2. https://ansm.sante.fr/uploads/2022/04/07/20220407-aac-rcp-pentaglobin.pdf?.
3. The, et al. The Harriet Lane Handbook, 23 Edition: South Asia Edition - E-Book. Elsevier Health Sciences, 20 June 2023.
4. Carlone G, Torelli L, Maestro A, Zanon D, Barbi E, Maximova N. Pentaglobin® Efficacy in Reducing the Incidence of Sepsis and Transplant-Related Mortality in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Study. J Clin Med. 2020 May 24;9(5):1592. doi: 10.3390/jcm9051592. PMID: 32456295; PMCID: PMC7291252.
5. Nassir KF, Al-Saddi YI, Abbas HM, Al Khames Aga QA, Al Khames Aga LA, Oudah AA. Pentaglobin (immunoglobulin M-enriched immunoglobulin) as adjuvant therapy for premature and very low-birth-weight neonates with sepsis. Indian J Pharmacol. 2021 Sep-Oct;53(5):364-370. doi: 10.4103/ijp.ijp_881_20. PMID: 34854404; PMCID: PMC8641746.
6. Domizi, R., Adrario, E., Damiani, E. et al. IgM-enriched immunoglobulins (Pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial. Ann. Intensive Care 9, 135 (2019). https://doi.org/10.1186/s13613-019-0609-5