Lecture 8 - Hyperimmunes PDF

HYPERIMMUNE IMMUNOGLOBULINS Mesuli Mhlongo, B. Pharm UKZN 4th Year Pharmacy Students Presentation October 2024  Objectives Hyperimmune Overview...

HYPERIMMUNE IMMUNOGLOBULINS Mesuli Mhlongo, B. Pharm UKZN 4th Year Pharmacy Students Presentation October 2024  Objectives Hyperimmune Overview Human Hepatitis B immunoglobulin Human Rabies Immunoglobulin Human Anti-D Immunoglobulin Human Tetanus Immunoglobulin Human Varicella Zoster Immunoglobulin UKZN 4th Year Pharmacy Students Presentation October 2024 List of hyperimmune products Hebagam® IM 100 IU/ml 2 ml amp Rabigam ® IM 150 IU/ml 2 ml amp Rhesugam IM 500 IU/ (100μg) 2 ml amp Tetagam IM 250 IU/2ml 2 ml amp Vazigam ® IM ≥100 IU/ml 2 ml amp UKZN 4th Year Pharmacy Students Presentation October 2024  NBI Manufacturing Overview UKZN 4th Year Pharmacy Students Presentation October 2024 Composition Rhesugam® IM Pooled human plasma sourced from healthy Rh- donors who have Ab’s to the Rh Ag (D antigen) Hebagam® IM Donors would include hospital staff Derived from donors with who receive routine vaccinations with a high level of immunity the Hepatitis B vaccine. Their bodies to a specific disease. produce antibodies to the vaccine and yield high titres to the HB antigen. Plasma raw material is usually obtained from Rabigam® IM plasmapheresis donors who have immunity to The rabies vaccination program the disease either because of vaccination (e.g. is run to enable us to have hepatitis B) or having recently recovered from plasma that contains high titres the disease (e.g. varicella-zoster). of the rabies antibody. UKZN 4th Year Pharmacy Students Presentation October 2024 General Notes Indications and guidelines for use, as per registered Professional Information Contain no antimicrobial preservative Stabilised with glycine (Rhesugam IM is stabilised with human albumin and glycine) UKZN 4th Year Pharmacy Students Presentation October 2024 Contraindications IM injections are not advocated for patients with bleeding disorders The risk-benefit ratio in patients with a history of IgA deficiency or severe anaphylactic reactions to plasma products should be considered The safety of immunoglobulins in pregnancy has not been established in controlled clinical trials The effect of live vaccines (measles, mumps, rubella and varicella) may be inhibited if immunoglobulins are given. They should not be administered until three months after the administration of immunoglobulins. UKZN 4th Year Pharmacy Students Presentation October 2024 Storage Instructions Transport within 72 hours below 37 °C. Store between 2 °C and 8 °C. Do not freeze. Protect from light. UKZN 4th Year Pharmacy Students Presentation October 2024  Hebagam® IM Human hepatitis B immunoglobulin for intramuscular injection T/30.2/746 UKZN 4th Year Pharmacy Students Presentation October 2024 Hepatitis Inflammation of liver Causes Viruses Alcohol Drugs/Chemicals/Poisons Acute Chronic Cirrhosis Liver failure UKZN 4th Year Pharmacy Students Presentation October 2024 UKZN 4th Year Pharmacy Students Presentation October 2024 Hepatitis B Chronic carriers Virus in body fluids Routes of transmission Perinatal Blood Sexual Prevention Vaccination Passive immunity UKZN 4th Year Pharmacy Students Presentation October 2024 Indications Post-exposure prophylaxis resulting from: needle stick injury mucosal exposure sexual exposure Newborn babies born to HBsAg/HBeAg-positive mothers At birth or within 48 hours for neonates Within 48 hours but not > 7 days At the same time as the first dose of hepatitis B vaccine UKZN 4th Year Pharmacy Students Presentation October 2024  Rabigam® IM Human rabies immunoglobulin for intramuscular injection T/30.2/748 UKZN 4th Year Pharmacy Students Presentation October 2024 Human Rabies Immunoglobulin Confers passive immunisation against rabies in all non-immunised persons known or suspected to have been exposed to the rabies virus. Indicated for post-exposure prophylaxis in all severe exposures classified as Category III Used in conjunction with the vaccine – active immunity Not indicated in patients with proven immunity (previously immunised) – these patients require booster dose of vaccine on Day 0 and day 3 only If indicated, use irrespective of time interval between exposure and initiation of treatment. However, it may only be used within 7 days of first dose of vaccine UKZN 4th Year Pharmacy Students Presentation October 2024  Rabigam® IM immunoglobulin is infiltrated into the wound and the remainder is administered IM at an anatomical site distant from where the rabies vaccine is administered. Rabies - 2 vaccines are given 1 month apart. One month later samples are taken to check the titre level. UKZN 4th Year Pharmacy Students Presentation October 2024 Incubation Period Varies from 5 days to >1 year (average 20 - 90 days) During most of incubation period, virus is in transport through axons During very long incubation periods (> 4 months), it is thought that the virus may remain latent at site of inoculation, before entering the peripheral nervous system Hence, the local infiltration of the wound site with rabies immunoglobulin is of utmost importance and helps prevent the formation of ‘reservoirs’ UKZN 4th Year Pharmacy Students Presentation October 2024 Incubation Period Length of incubation period depends on: Severity and/or size and/or depth of bite or scratch: The higher the dose of virus introduced, the greater the possibility of disease development, and the incubation period is shorter Age / size of patient: Children have shorter incubation periods, due to their smaller body surface areas as well as shorter afferent nerves Location of bite: Incubation period is shorter for bites close to CNS (face, neck, head) UKZN 4th Year Pharmacy Students Presentation October 2024 Assessment of Exposure Ideally, post exposure prophylaxis should be administered to all Category III bite victims Constraints in SA (as in many other countries): Cost of PEP – In SA, the state covers cost for eligible patients. Private sector patients are covered by their medical aid. Intermittent availability of immunoglobulin and vaccine Lack of awareness of rabies prevention guidelines Failed post-exposure prophylaxis due to various reasons, e.g., non-completion of vaccine schedule (largely attributed to socio-economic constraints.) UKZN 4th Year Pharmacy Students Presentation October 2024 Post-exposure Prophylaxis Prompt local wound care Irrigate/ flush/ wash wound thoroughly under running water with soap/detergent or saline or chlorhexidine or cetrimide, for minimum of 5 minutes Apply disinfectant, e.g. Betadine or aqueous iodine Do not suture or apply compressive bandages, if possible Rabies vaccine Inject single dose vaccine into deltoid muscle on days 0, 3, 7, and 14 Previously immunised patients: inject single dose vaccine into deltoid muscle on days 0 and 3 only Rabies immunoglobulin Unimmunised patient: Infiltrate immunoglobulin (20 IU/kg) on day 0, in and around the wound, with remainder into nearest deltoid – opposite to that used for vaccine administration. Immunocompromised patients may require rabies immunoglobulin for Category II exposures Additional treatments Tetanus toxoid to be given if necessary (if ≥ 5 years after primary immunization) Broad spectrum antibiotic as indicated UKZN 4th Year Pharmacy Students Presentation October 2024  Rhesugam® IM Human Anti-D (Rh) immunoglobulin Solution for intramuscular injection T/30.2/750 UKZN 4th Year Pharmacy Students Presentation October 2024 Mechanism of Action: HDN UKZN 4th Year Pharmacy Students Presentation October 2024 Haemolytic Disease of the Newborn Maternal anti-D frequent cause of HDN (HDFN) First reported 1609 by French midwife Dramatic and significant decrease in cases since introduction of Anti-D Immunoglobulin prophylaxis in 1968-1970 But HDN does still occur! KwaZulu-Natal approx.100 antibody cases/year UKZN 4th Year Pharmacy Students Presentation October 2024 Features and Management Jaundice, hepatosplenomegaly, hydrops fetalis, anaemia Treatment options Phototherapy Exchange transfusion IVIG UKZN 4th Year Pharmacy Students Presentation October 2024 Prevention of HDN Programme Aim: Prevent HDN due to Anti-D as far as possible by: Identifying the Rh-negative antenatal patients and Administering Anti-D Immunoglobulin. UKZN 4th Year Pharmacy Students Presentation October 2024 Anti-D Pharmacology and Uses Prevents active immunisation to the Rh (D) erythrocyte antigen in Rh- negative individuals exposed to Rh positive blood Most important application: Prevention of HDN UKZN 4th Year Pharmacy Students Presentation October 2024 Indications Abortions During pregnancy after any potentially sensitising event: 250 IU 4 ml additional anti-D should be given UKZN 4th Year Pharmacy Students Presentation October 2024 Other Indications Transfusion of Rh-positive blood 25 µg / ml of RBC Require approx. 50 ampoules for 500 ml blood transfusion!!! UKZN 4th Year Pharmacy Students Presentation October 2024 Contraindications Rh positive women Rh negative women who have been sensitised to the D antigen Rh negative women carrying or delivered a Rh negative infant Not for the infant !!!! UKZN 4th Year Pharmacy Students Presentation October 2024 Rapid Rh Kit Quick screening, highly sensitive and specific test Establish Rh type of patient Single drop of whole blood Red cell agglutination test Rh-negative further blood sample specimen taken for confirmation UKZN 4th Year Pharmacy Students Presentation October 2024  Tetagam® IM Human Tetanus immunoglobulin UKZN 4th Year Pharmacy Students Presentation October 2024 Tetanus : Clinical Features, Prophylaxis & Treatment Tetanus typically arises from a skin wound that becomes contaminated by a bacterium called Clostridium tetani, which is often found in soil. UKZN 4th Year Pharmacy Students Presentation October 2024 Clinical Features It is characterised by: an acute onset of hypertonia Painful muscular contractions (usually of the muscles of the jaw and neck), Generalised muscle spasms without other apparent medical causes. Once the bacteria are in the body, they produce a neurotoxin The neurotoxin is known as tetanospasmin and this causes the muscle spasms Tetanospasmin can travel throughout the body via the bloodstream, lymph system and nerves, leading to generalised muscle spasms UKZN 4th Year Pharmacy Students Presentation October 2024 Additional Treatment Measures for Clinical Tetanus For contaminated wounds or wounds with much devitalised tissue, tetanus immunoglobulin and tetanus toxoid are required as adjuncts to other essential measures: Adequate debridement of wound as the dirt and dead tissue promote multiplication of C. tetani Physiological support - maintenance of airway, fluid balance, nursing care Drug control of convulsions Appropriate antibiotic therapy UKZN 4th Year Pharmacy Students Presentation October 2024  Without treatment, tetanus can be fatal UKZN 4th Year Pharmacy Students Presentation October 2024 Tetagam® IM Derived from pooled plasma from healthy donors Contain a high titre of antibodies to the tetanus toxin Available as a solution for intramuscular injection Tetagam® IM 250 IU/2 ml contains 125 IU/ml tetanus antibodies UKZN 4th Year Pharmacy Students Presentation October 2024 Mechanism of Action Antibody-antigen reaction resulting in the neutralisation of the toxin Role is two-fold – prophylaxis/prevention – treatment of clinical tetanus, both locally by infiltration into the wound site, as well as intramuscularly UKZN 4th Year Pharmacy Students Presentation October 2024 Tetanus Prophylaxis Prophylactic treatment is given Susceptibility of wounds to to patients with suspected contamination should be Clostridium tetani exposure characterised according to: a) The type and condition b) The patient’s of the wound: Tetanus-prone immunisation history: wounds: contaminated with dirt, Administration of tetanus faeces, soil, etc., puncture immunoglobulin and tetanus wounds, avulsions and wounds toxoid are considered, based on resulting from missiles, crushing, the patient’s immune status. burns and frostbite. UKZN 4th Year Pharmacy Students Presentation October 2024 Dosage and Directions for Use Prophylaxis: High risk injuries to non-immune and immune patients 250 IU in patients 10 years and older (500 IU if 24 hrs have past since injury, or if there is a risk of heavy contamination) Treatment: Clinical Tetanus 3000 IU – 6000 IU as a single dose UKZN 4th Year Pharmacy Students Presentation October 2024  Vazigam® IM Human varicella-zoster immunoglobulin for intramuscular injection UKZN 4th Year Pharmacy Students Presentation October 2024 Indications Confers passive immunity against chickenpox High risk patients Premature neonates Immunocompromised patients HIV positive symptomatic, immunosuppressive therapy Neonates 5 days before or 48 hours after delivery Bone marrow recipients Not for treatment of chickenpox or shingles UKZN 4th Year Pharmacy Students Presentation October 2024 Chicken-pox COMMON SPREADS VIA CONTAGIOUS DISEASE – THE AIR PERIOD - ~2 CAUSED BY THROUGH DAYS BEFORE VARICELLA- COUGHS AND RASH APPEARS ZOSTER VIRUS SNEEZES OR AND LASTS OF THE HERPES THROUGH UNTIL ALL VIRUS FAMILY CONTACT WITH BLISTERS HAVE FLUID FROM CRUSTED INSIDE THE OVER. CHICKEN-POX BLISTERS UKZN 4th Year Pharmacy Students Presentation October 2024 Dosage and Directions for Use Prophylaxis: > 15 IU/kg body weight as soon as possible, but not more than 96 hours after exposure. Alternative recommended doses for treatment are as follows: * 2 ml for patients up to 5 years; * 4 ml for patients aged 6 to 10 years; * 5 ml for patients aged 11 to 14 years; * 6 ml for patients 15 years and older. UKZN 4th Year Pharmacy Students Presentation October 2024 Case Evaluation in Periods of Plasma Shortage Base decision to use on susceptibility exposure risk of complications Administered within 96 hours of exposure Reserve for high-risk patients UKZN 4th Year Pharmacy Students Presentation October 2024