7.2 drug-laboratory interactions: serological testing antibodies present in hepagam b may interfere with some serological tests. after administration of immune globulins like hepagam b, a transitory increase of passively transferred antibodies in the patient’s blood may result in misleading positive results in serological testing (e.g. coombs' test). 7.3 drug-laboratory interactions: blood glucose testing hepagam b contains maltose which can interfere with certain types of blood glucose monitoring systems. [see warnings and precautions ( 5.2 ) .] only testing systems that are glucose-specific should be used in patients receiving hepagam b. this interference can result in falsely elevated glucose readings that can lead to untreated hypoglycemia or to inappropriate insulin administration, resulting in life-threatening hypoglycemia. the product information of the blood glucose testing system, including that of the test strips, should be carefully reviewed to determine if the system is appropriate for use with maltose-containing parenteral products. if any uncertainty exists, contact the manufacturer of the testing system to determine if the system is appropriate for use with maltose-containing parenteral products.

d exposure to persons with acute hbv infection.

n iga deficient patients with antibodies against iga and history of hypersensitivity reaction. (see contraindications [ 4 ]) 5.2 interference with blood glucose testing the maltose contained in hepagam b can interfere with some types of blood glucose monitoring systems, i.e., those based on the glucose dehydrogenase pyrroloquine quinone (gdh-pqq) method. this can result in falsely elevated glucose readings and, consequently, in the inappropriate administration of insulin, resulting in life-threatening hypoglycemia. cases of true hypoglycemia may go untreated if the hypoglycemic state is masked by falsely elevated results. 5.3 monitoring: serum anti-hbs antibody levels liver transplant patients should be monitored regularly for serum anti-hbs antibody levels using a quantitative assay to ensure that adequate protective levels are maintained. 5.4 infusion reactions certain adverse drug reactions may be related to the rate of infusion. the recommended infusion rate given under dosage and administration ( 2.1 ) must be closely followed. patients must be closely monitored and carefully observed for any symptoms throughout the infusion period and immediately following an infusion. 5.5 transmissible infectious agents because hepagam b is made from human plasma, it may carry a risk of transmitting infectious agents, e.g. viruses, and, theoretically, the creutzfeldt-jakob disease (cjd) agent. no cases of transmission of viral diseases or cjd have been associated with the use of hepagam b. all infections suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to saol therapeutics at 1-877-443-0224. 5.6 coagulation disorders for postexposure prophylaxis indications, hepagam b must be administered intramuscularly only. in patients who have severe thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections, hepagam b should be given only if the expected benefits outweigh the potential risks. 5.7 thrombotic events thrombotic events may occur during or following treatment with igiv products 4, 5 . patients at risk include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization, and/or known/suspected hyperviscosity. consider baseline assessment of blood viscosity in patients at risk for hyperviscosity including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies. for patients who are at risk of developing thrombotic events, administer hepagam b at the minimum rate of infusion practicable.

exual exposure to hbsag-positive persons 0.06 milliliter per kilogram administer hepagam b within 14 days of the last sexual contact or if sexual contact with the infected person will continue household exposure to persons with acute hbv infection 0.5 milliliter infants less than 12 months: administer hepagam b + hepatitis b vaccine if primary caregiver has acute hbv infection. 2.1 prevention of hepatitis b recurrence following liver transplantation administer the first dose of hepagam b during the grafting of the transplanted liver (the anhepatic phase) with subsequent dosing as recommended in table 1 . calculate the dosing from the measured potency of the particular lot of hepagam b as stamped on the vial label. administer by intravenous infusion ( table 2 ). table 1 - hepagam b dosing regimen for hbv-related liver transplant patients * each dose should contain 20,000 international units calculated from the measured potency as stamped on the vial label [ see dosage forms and strengths ( 3 ) ]. anhepatic phase week 1 post-operative weeks 2-12 post-operative month 4 onwards first dose daily from day 1-7 every two weeks from day 14 monthly table 2 – hepagam b intravenous infusion rate route of administration dosage infusion rate intravenous 20,000 international units per dose 2 milliliters per minute. decrease to 1 milliliter per minute or slower if the patient develops discomfort or infusion-related adverse reactions. hepagam b dose adjustments may be required in patients who fail to reach anti-hbs levels of 500 international units per liter within the first week post-liver transplantation 1 . patients who have surgical bleeding or abdominal fluid drainage (greater than 500 milliliters) or patients who undergo plasmapheresis are particularly susceptible to extensive loss of circulated anti-hbs. in these cases, the dosing regimen should be increased to a half-dose (10,000 international units calculated from the measured potency as stamped on the vial label) intravenously every 6 hours until the target anti-hbs is reached. 2.2 postexposure prophylaxis administer hepagam b intramuscularly as recommended in table 3 . table 3 – hepagam b dosing regimen for postexposure prophylaxis (intramuscular) indication dosage instructions acute exposure to blood containing hbsag 0.06 milliliter per kilogram administer hepagam b as soon as possible after exposure. the value after seven days following exposure is unclear 2, 3 .for persons who refuse hepatitis b vaccine or who are known non-responders to vaccine, give a second dose of hepagam b one month after the first dose 2 . perinatal exposure of infants born to hbsag-positive mothers 0.5 milliliter administer after physiologic stabilization of the infant and preferably within twelve hours of birth. administer concurrently with hepatitis b vaccine. sexual exposure to hbsag-positive persons 0.06 milliliter per kilogram administer hepagam b and hepatitis b vaccine series within 14 days of sexual contact or if sexual contact with the infected person will continue. household exposure to person with acute hbv infection 0.5 milliliter for infants less than twelve months of age administered concurrently with hepatitis b vaccine. prophylaxis of other household contacts of persons with acute hbv infection is not indicated unless there is an identifiable blood exposure to the index patient, such as by sharing toothbrushes or razors. treat such exposures like sexual exposures. hepagam b may be administered at the same time (but at a different site), or up to one month preceding hepatitis b vaccination without impairing the active immune response to hepatitis b vaccine 2,3 . 2.3 preparation parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. do not use if turbid. do not shake vials during preparation to avoid foaming. the hepagam b vial is for single use only. hepagam b contains no preservatives. promptly use any vial of hepagam b that has been entered. do not reuse or save for future use. for intravenous administration, administer hepagam b through a separate intravenous line using an infusion pump. use normal saline as the diluent if dilution of hepagam b is preferred prior to intravenous administration. [ see clinical trials in liver transplant patients ( 14.1 )] do not use dextrose (5%) in water (d5w). use a separate vial, sterile syringe, and needle for each individual patient, to prevent transmission of infectious agents from one person to another.

( 2.1 ) ]. the attributed adverse drug reaction of hypotension was reported in one patient. the reaction was associated with a single hepagam b infusion during the first day post-transplant. the reaction resolved on the same day and did not recur with subsequent hepagam b infusions. healthy volunteer studies seventy healthy male and female volunteers received a single dose of hepagam b intramuscularly in clinical trials 6 . only one adverse drug reaction, an episode of nausea, was reported. 6.2 postmarketing experience the following adverse reactions have been identified during postapproval use of hepagam b. because these reactions 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. postexposure prophylaxis: dizziness has been reported in the postmarketing surveillance of hepagam b for the postexposure prophylaxis indication. hepatitis b-related liver transplantation: the system organ classification of reported adverse reactions is provided below: cardiac disorders: sinus tachycardia gastrointestinal disorders: abdominal pain upper nausea general disorders and administration site conditions: chills feeling cold influenza like illness pyrexia immune system disorders: anaphylactoid reaction hypersensitivity investigations: lipase increased transaminases increased musculoskeletal and connective tissue disorders: back pain nervous system disorders: dizziness headache respiratory, thoracic and mediastinal disorders: dyspnoea skin and subcutaneous tissue disorders: cold sweat healthcare professionals should report adverse reactions following the administration of hepagam b to saol therapeutics at 1-833-644-4216 or fda’s medwatch reporting system at 1-800-fda-1088 or www.fda.gov/medwatch .

7.2 drug-laboratory interactions: serological testing antibodies present in hepagam b may interfere with some serological tests. after administration of immune globulins like hepagam b, a transitory increase of passively transferred antibodies in the patient’s blood may result in misleading positive results in serological testing (e.g. coombs' test). 7.3 drug-laboratory interactions: blood glucose testing hepagam b contains maltose which can interfere with certain types of blood glucose monitoring systems. [see warnings and precautions ( 5.2 ) .] only testing systems that are glucose-specific should be used in patients receiving hepagam b. this interference can result in falsely elevated glucose readings that can lead to untreated hypoglycemia or to inappropriate insulin administration, resulting in life-threatening hypoglycemia. the product information of the blood glucose testing system, including that of the test strips, should be carefully reviewed to determine if the system is appropriate for use with maltose-containing parenteral products. if any uncertainty exists, contact the manufacturer of the testing system to determine if the system is appropriate for use with maltose-containing parenteral products.

ver to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

other licensed comparator hepatitis b immune globulin (human) products 6 . comparability of pharmacokinetics between hepagam b and a commercially available hepatitis b immune globulin product administered im indicates that comparable efficacy of hepagam b should be inferred.

able efficacy of hepagam b should be inferred.

ent group, hepagam b intravenous doses of 35 milliliters were initiated during transplant according to the regimen identified in table 1 [see dosage and administration ( 2.1 ) ]. as a result of the targeted potency of 550 international units per milliliter at the time of manufacture [see dosage forms and strengths ( 3. ) ], the 35 milliliter doses of hepagam b used in this study actually contained between 17,000 and 23,000 international units anti-hbs. these 35 milliliter doses consistently yielded anti-hbs trough levels greater than 500 international units per liter (99% of all anti-hbs levels were greater than 500 international units per liter; see figure 1 ). patients received hepagam b doses diluted with 50 milliliters of saline. figure 1: frequency histogram of trough anti-hbs levels more than 30 days after transplant values below the target trough were only observed in the 2 patients with hbv recurrence who had anti-hbs levels less than 150 international units per liter at the time of seroconversion. for the efficacy endpoint of the proportion of patients with hbv recurrence (hbsag positive and/or hbeag positive after 4 weeks post-olt), a significant treatment effect was observed. as summarized in table 5 , hbv recurrence was seen in 2/24 or 8.3% of hepagam b patients compared to 12/14 or 86% of retrospective untreated control patients (see table 5 ). two of the hepagam b patients who died within 28 days post-transplant were excluded from all efficacy analyses, but included for safety analyses. the deaths were not hbv or study drug related. table 5 - results of study hb-005 for the prevention of hepatitis b recurrence following liver transplantation hepagam b retrospective untreated control p-value (fisher's exact test) hbv recurrence proportion, % (95% confidence interval) 8.3 (0.1 -27.0) 85.7 (57.2 -98.2) less than 0.001 the conclusion that hepagam b monotherapy post-olt is effective at preventing hbv recurrence post-olt is further supported by the secondary endpoints of time to recurrence, survival, anti-hbs levels, biochemical markers of liver inflammation, and liver biopsy. time to recurrence for the hepagam b treatment group was 358 days for two hbv recurrent patients. in comparison, the retrospective untreated control patients had a median time to recurrence of 88 days with a 95% confidence interval of 47 to 125 days. survival calculations showed that 96% (23/24) of patients in the active treatment group survived for at least 1 year post-olt compared to 43% (6/14) retrospective control patients. the endpoints for hbv recurrence were supported by an observed drop in anti-hbs levels, elevated liver function tests, and abnormal liver biopsy result at the time of recurrence. hepagam b is recommended in patients who have no or low levels of viral replication at the time of liver transplantation. the clinical trial evaluating hepagam b in liver transplant patients selected patients with no or low replication status only. hepagam b therapy has not been evaluated in combination with antiviral therapy post-transplantation. figure 1

ially life threatening allergic reactions. in case of allergic or anaphylactic reaction, the infusion should be stopped immediately. in case of shock, the current medical standards for treatment of shock should be observed. advise liver transplant patients about the potential interference with non-glucose specific monitoring systems. the maltose contained in hepagam b can interfere with some types of blood glucose monitoring systems. only testing systems that are glucose-specific should be used in patients receiving hepagam b. this inference can result in falsely elevated glucose readings that can lead to untreated hypoglycemia or to inappropriate insulin administration, resulting in life-threatening hypoglycemia. hepagam b ® [hepatitis b immune globulin intravenous (human)] sterile solution for injection and any and all saol brand, product, service and feature names, logos, slogans are trademarks or registered trademarks of saol. all rights reserved. planova ® is a registered trademark of asahi kasei medical co., ltd, triton ® is a registered trademark of union carbide corporation. novaplus is a registered trademark of vizient, inc. distributed by: saol therapeutics inc. roswell, ga 30076 u.s. license no. 2098 part no: 1003067