Posology : מינונים

5. DOSAGE AND ADMINISTRATION
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration; if these are seen, vials should not be used. During preparation, do not shake vials; avoid foaming.
The HepaGam B™ vial is for single use only. Any vial of HepaGam B™ that has been entered should be used promptly. Do not reuse or save for future use. This product contains no preservative; therefore, partially used vials should be discarded immediately.
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. Do not use dextrose (5%) in water (D5W).
It is important to use a separate vial, sterile syringe, and needle for each individual patient, to prevent transmission of infectious agents from one person to another.

Prevention of Hepatitis B recurrence following liver transplantation
For the prevention of hepatitis B recurrence following liver transplantation in HBsAg positive liver transplant patients, in adults: 10,000 IU on the day of transplantation, peri-operatively then 2,000-10,000 IU/day for 7 days, and as necessary to maintain antibody levels above 100-150 IU/l in HBV-DNA negative patients and above 500 IU/l in HBV-DNA positive patients.
The first dose should be administered concurrently with the grafting of the transplanted liver (the anhepatic phase) with subsequent dosing as recommended in Table 2.

Table 2 - HepaGam B™ Dosing Regimen
Anhepatic Phase       Week 1 Post-Operative HBV-DNA negative                      HBV-DNA positive patients ** patients**

First dose                 Daily 2000 to 10000 IU Maintain anti-HBs titers   Maintain anti-HBs titers >500 for the first 7 days    >100 to 150 mIU/mL        mIU/mL
**Regular monitoring of serum HBsAg and levels of anti-HBs antibody should be performed pre-infusion to track treatment response and allow for treatment adjustment.

HepaGam B™ dose adjustments may be required in patients who fail to reach anti-HBs levels of 100-150 mIU/mL within the first week post-liver transplantation. Patients who have surgical bleeding or abdominal fluid drainage (> 500 mL) 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 (≥ 5,000 IU) intravenously every 6 hours until the target anti-HBs is reached.
Hepatitis B Immunoglobulin (HBIG) products are most effective in patients with no or low levels of HBV replication at the time of transplantation.
HepaGam B™ should be prepared for intravenous administration under aseptic conditions. HepaGam B™ should be administered through a separate intravenous line using an intravenous administration set via infusion pump.
The rate of administration should be set at 2 mL per minute. The rate of infusion should be decreased to 1 mL per minute or slower if the patient develops discomfort, infusion-related adverse events or there is concern about the speed of infusion.

Postexposure Prophlyaxis
For postexposure prophylaxis indications, HepaGam B™ must be administered intramuscularly only as directed below.
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.

Acute Exposure to Blood Containing HBsAg:
Table 3 summarizes prophylaxis for percutaneous (needlestick, bite, sharps), ocular, or mucous membrane exposure to blood according to the source of exposure and vaccination status of the exposed person. For greatest effectiveness, passive prophylaxis with HepaGam B™ should be given as soon as possible after exposure, as its value after seven days following exposure is unclear. An injection of 0.06 mL/kg of body weight should be administered intramuscularly as soon as possible after exposure, and within 24 hours if possible. Consult the Hepatitis B Vaccine package insert for dosage information regarding the vaccine.
For persons who refuse Hepatitis B Vaccine or are known non-responders to vaccine, a second dose of HepaGam B™ should be given one month after the first dose.

Table 3 - Recommendations for Hepatitis B Prophylaxis Following Percutaneous or Permucosal Exposure
Source                                          Exposed Person
Unvaccinated                                         Vaccinated
HBsAg-positive 1. Hepatitis B Immunoglobulin Intravenous         1. Test exposed person for anti-HBs (Human) (HBIGIV) x 1 immediately*                 2. If inadequate antibody‡, Hepatitis B 2. Initiate HB vaccine series†                    Immunoglobulin Intravenous (Human) x 1 immediately plus either HB vaccine booster dose,
or a second dose of HBIGIV*, 1 month later§
Known Source – 1. Initiate HB vaccine series                     1. Test source for HBsAg only if exposed is vaccine High Risk for    2. Test source of HBsAg. If positive, Hepatitis nonresponder; if source is HBsAg-positive, give HBsAg-positive B Immunoglobulin Intravenous (Human)              Hepatitis B Immunoglobulin Intravenous (Human) x (HBIGIV) x 1                                    1 immediately plus either HB vaccine booster dose, or a second dose of HBIGIV*, 1 month later§
Known Source – Initiate HB vaccine series                        Nothing required Low Risk for
HBsAg-positive
Unknown Source Initiate HB vaccine series                        Nothing required * Hepatitis B Immunoglobulin Intravenous (Human) dose of 0.06 mL/kg I.M.
† See manufacturers’ recommendation for appropriate dose.
‡ Less than 10 mIU/mL anti-HBs by radioimmunoassay, negative by enzyme immunoassay.
§ Two doses of Hepatitis B Immunoglobulin Intravenous (Human) is preferred if no response after at least four doses of vaccine.

Prophylaxis of Infants Born to Mothers who are Positive for HBsAg with or without HBeAg: Table 4 contains the recommended schedule of Hepatitis B prophylaxis for infants born to mothers that are either known to be positive for HBsAg or have not been screened. Infants born to mothers known to be HBsAg-positive should receive 0.5 mL HepaGam B™ after physiologic stabilization of the infant and preferably within 12 hours of birth. The Hepatitis B Vaccine series should be initiated simultaneously, if not contraindicated, with the first dose of the vaccine given concurrently with the HepaGam B™, but at a different site. Subsequent doses of the vaccine should be administered in accordance with the recommendations of the manufacturer.
Women admitted for delivery, who were not screened for HBsAg during the prenatal period, should be tested.
While test results are pending, the newborn infant should receive Hepatitis B Vaccine within 12 hours of birth (See manufacturers’ recommendations for dose). If the mother is later found to be HBsAg-positive, the infant should receive 0.5 mL HepaGam B™ as soon as possible and within seven days of birth; however, the efficacy of HepaGam B™ administered after 48 hours of age is not known. Testing for HBsAg and anti-HBs is recommended at 12-15 months of age. If HBsAg is not detectable and anti-HBs is present, the child has been protected.

Table 4 - Recommended Schedule of Hepatitis B Immunoprophylaxis to Prevent Perinatal Transmission of Hepatitis B Virus Infection
Age of Infant
Infant born to mother known to be HBsAg- Infant born to mother not screened for HBsAg Administer                          positive
First Vaccination*             Birth (within 12 hours)                          Birth (within 12 hours) Hepatitis B                Birth (within 12 hours)                If mother is found to be HBsAg-positive, Immunoglobulin                                                     administer dose to infant as soon as possible, Intravenous                                                             not later than 1 week after birth (Human)†
Second Vaccination*                     1 month                                        1-2 months Third Vaccination*                     6 months                                        6 months * See manufacturers’ recommendations for appropriate dose.
† 0.5 mL administered I.M. at a site different from that used for the vaccine.

Sexual Exposure to HBsAg-positive Persons:
All susceptible persons whose sexual partners have acute hepatitis B infection should receive a single dose of HepaGam B™ (0.06 mL/kg) and should begin the Hepatitis B Vaccine series, if not contraindicated, within 14 days of the last sexual contact or if sexual contact with the infected person will continue. Administering the vaccine with HepaGam B™ may improve the efficacy of post exposure treatment. The vaccine has the added advantage of conferring long-lasting protection.

Household Exposure to Persons with Acute HBV Infection:
Prophylaxis of an infant less than 12 months of age with 0.5 mL HepaGam B™ and Hepatitis B Vaccine is indicated if the mother or primary caregiver has acute HBV infection. Prophylaxis of other household contacts of persons with acute HBV infection is not indicated unless they had an identifiable blood exposure to the index patient, such as by sharing toothbrushes or razors. Such exposures should be treated like sexual exposures. If the index patient becomes an HBV carrier, all household contacts should receive Hepatitis B Vaccine.