Hepatitis A Immune Globulin:

Aetna considers hepatitis A immune globulin medically necessary for members who are exposed or likely to be exposed to hepatitis A virus (HAV).  Risk groups include household and sexual contacts of persons with hepatitis A, newborn infants of HAV-infected mothers, staff* and children at child-care centers and schools with HAV outbreaks, staff* of custodial care institutions with HAV outbreaks, and individuals exposed to HAV through food or waterborne outbreaks. 

Aetna considers hepatitis A immune globulin experimental and investigational for other indications because of insufficient evidence of safety and effectiveness.

Hepatitis B Immune Globulin:

Aetna considers hepatitis B immune globulin medically necessary for members who have had contact with an individual diagnosed with hepatitis B virus (HBV).  Risk groups include infants born to hepatitis B surface antigen (HBsAg)-positive mothers, persons with percutaneous or permucosal exposure to HbsAg-positive blood, sexual contacts of HbsAg-positive persons, and household exposure of infants less than 1 year of age to a primary caregiver with acute HBV infection. 

Aetna considers prolonged use of hepatitis B immune globulin medically necessary for prophylaxis of recurrent hepatitis B infection in HbsAg-positive liver transplant recipients.  

Aetna considers hepatitis B immune globulin experimental and investigational for other indications because of insufficient evidence of safety and effectiveness.

Cytomegalovirus Immune Globulin:

Aetna considers cytomegalovirus (CMV) immune globulin (e.g., Cytogam) medically necessary for members who have had definite symptoms or exposure to cytomegalovirus.  Cytomegalovirus immune globulin is also considered medically necessary for prophylaxis or treatment of CMV disease in CMV-negative renal transplant members receiving a CMV-positive donor organ, and for prophylaxis and treatment of CMV disease in other transplant recipients.

Aetna considers the use of CMV immune globulin experimental and investigational for all other indications, including use in prophylaxis of persons with IgA deficiency or Waldenstrom's macroglobulinemia, treatment of in-utero cytomegalovirus infection because of insufficient evidence of its safety and effectiveness.

See also CPB 0206 - Parenteral Immunoglobulins.

Rho-D Immune Globulin:

Aetna considers Rho-D Immune Globulin (e.g., Gamulin Rh, HypRho-D Full Dose, HypRho-D Mini-Dose, MICRhoGAM, Mini-Gamulin Rh, Rhogam, and WinRho SDF) medically necessary for preventing hemolytic disease of the newborn.  Rho-D immune globulin is considered medically necessary for all unsensitized Rh-negative women at 24 to 28 weeks gestation, unless the father is known to be Rh-negative.  A repeat post-partum dose is considered medically necessary if a Rh-positive infant is delivered.  Administration of Rho-D immune globulin is considered medically necessary in unsensitized Rh-negative women, unless the father is known to be Rh-negative, after other obstetric complications such as amniocentesis, chorionic villus sampling, ectopic pregnancy, pregnancy termination (including elective abortion), cordocentesis, fetal surgery or manipulation (including external version), antepartum placental hemorrhage, ante-partum fetal death, miscarriage and stillbirth.  Rho-D immune globulin is also considered medically necessary for treatment of Rho-D positive persons with idiopathic thrombocytopenic purpura.

Aetna considers Rho-D immune globulin experimental and investigational for other indications because of insufficient evidence of its safety and effectiveness.

Rabies Immune Globulin:

Aetna considers rabies immune globulin medically necessary for treatment of rabies exposure where the animal has escaped or is known to be rabid at the time of direct exposure or attack*.  

Aetna considers rabies immune globulin experimental and investigational for other indications because of insufficient evidence of its safety and effectiveness.

Varicella Zoster (Chickenpox) Immune Globulin:

Aetna considers varicella zoster immune globulin (VZIG) medically necessary for prevention of varicella (chickenpox) infections in high-risk individuals who have significant exposure to the disease due to contact with an individual who is infected with varicella, according to recommendations of the American Academy of Pediatrics.  High-risk individuals include immunocompromised persons without a history of chickenpox, susceptible pregnant women, newborn infants whose mother had onset of chickenpox within the 5 days before delivery or within 48 hours after delivery, hospitalized premature infants 28 or more weeks gestation whose mother has no history of chickenpox, and hospitalized premature infants less than 28 weeks gestation regardless of maternal history.  Significant exposures include household contacts of infected persons, face-to-face indoor play with infected persons, hospital contact with infected persons, and newborn infants whose mothers had onset of chickenpox near time of delivery (described above). 

Aetna considers VZIG experimental and investigational for other indications because of insufficient evidence of its safety and effectiveness.

Tetanus Immune Globulin:

Aetna considers intra-muscular injection of tetanus immune gamma globulin medically necessary for prevention of tetanus in non-immunized persons, incompletely immunized persons (who have not completed the 3-dose primary vaccination series), and remotely immunized persons (last complete vaccination more than 10 years ago) with neglected or tetanus-prone wounds (contaminated, necrotizing, or puncture wounds)*.  

Aetna considers tetanus immune globulin experimental and investigational for other indications because of insufficient evidence of its safety and effectiveness.

Rubeola (Measles) Immune Globulin:

Aetna considers intramuscular injection of measles (rubeola) immune globulin medically necessary for unvaccinated individuals exposed to the disease. 

Aetna considers rubeola immune globulin experimental and investigational for other indications because of insufficient evidence of its safety and effectiveness.

Immune Globulin (IVIG) for German Measles (Rubella):

Aetna considers non-specific intravenous immune globulin (IVIG) medically necessary for non-immune women with documented exposure to rubella during the first trimester (3 months) of pregnancy.  

Aetna considers IVIG for rubella experimental and investigational when these criteria are not met because of insufficient evidence of its safety and effectiveness.

Respiratory Syncytial Virus (RSV) Immune Globulin or Palivizumab:

See CPB 0318 - Synagis (palivizumab) for Prevention of Respiratory Syncytial Virus (RSV) Infections.

Vaccinia (Smallpox) Immune Globulin:

Aetna considers vaccinia vaccine medically necessary for treatment of vaccine complications with severe clinical manifestations (e.g., eczema vaccinatum, progressive vaccinia, severe generalized vaccinia, and severe ocular viral implantation).* 

Aetna considers vaccinia immune globulin experimental and investigational for other indications because of insufficient evidence of its safety and effectiveness.  See also CPB 0644 - Smallpox Vaccine.

Infantile Botulism Immune Globulin:

Aetna considers human-derived botulinum immune globulin (BabyBIG or BIG-IV) for the treatment of infant botulism caused by toxin types A or B in members below 1 year of age medically necessary.

Aetna considers human-derived botulinum immune globulin (BabyBIG or BIG-IV) experimental and investigational for other indications because of insufficient evidence of its safety and effectiveness.

Immune Globulin IM (GamaSTAN S/D (formerly BayGam))

Aetna considers immune globulin IM (IGIM) medically necessary for the following indications:

1. Hepatitis A. The prophylactic value of IGIM is greatest when given before or soon after exposure to hepatitis A. IGIM is considered experimental and investigational for individuals with clinical manifestations of hepatitis A or in those exposed more than 2 weeks previously; or
2. Measles (rubeola), for the prevention or modification of measles in susceptible contacts (one who has not been vaccinated and has not had measles previously) exposed less than 6 days previously. Note: IGIM should not be given with measles vaccine.
3. Immunoglobulin deficiency, to prevent serious infection if circulating IgG levels of approximately 200 mg/dL plasma are maintained; or
4. Varicella, prevention in immunosuppressed persons, if varicella zoster immune globulin is unavailable.. Note: Passive immunization against varicella in immunosuppressed persons is best accomplished with varicella-zoster immune globulin.

Aetna considers IGIM experimental and investigational for rubella prophylaxis. The routine use of IGIM for rubella prophylaxis in early pregnancy is of dubious value and cannot be justified. 

*Note: Treatment of work-related injuries is excluded from coverage under some benefit plans.  Please check benefit plan descriptions.  Work-related injuries may be covered by the employer's workman's compensation benefit plan.

Cytomegalovirus Immune Globulin

Cytomegalovirus Immune Globulin IV (CMV-Ig) is an injectable product that contains antibodies directed specificially towards cytomegalovirus (CMV), which is generally present in persons who have been exposed to the virus.  While CMV is quite prevalent in adults and is typically benign in healthy people, it is a significant cause of morbidity and mortality in people who are immunosuppressed due to organ transplantation or AIDS.

Cytomegalovirus Immune Globulin IV is currently approved by the Food and Drug Administration (FDA) for use in prevention and attentuation of CMV disease in renal transplant patients.  It also has been shown to be beneficial in prevention and treatment of CMV disease in patients who have received an orthotopic liver transplant.  There is also evidence for use of CMV-Ig in other solid organ transplants (such as heart and lung) and in bone marrow transplants.

Studies in renal transplantation have generally been limited to patients who are CMV sero-negative; use in sero-positive recipients therefore remains investigational.  This is not the case with other transplants; in fact, results in liver transplant patients have shown a decrease in severe CMV-associated syndromes.

In a retrospective analysis, Buxmann et al (2012) examined the current prenatal "off-label use" of CMV-hyperimmune globulin (CMV-HIG) in the prevention and treatment of congenital CMV (cCMV) infection, including the long-term outcome of the children.  This retrospective observational study comprised mothers and their children, born between January 1, 2006, and October 30, 2010.  Prenatal CMV-HIG was administered after diagnosis of primary CMV infection of the mother.  Clinical and virological data were collected from maternal and pediatric medical and laboratory reports.  Follow-up was 12 to 36 months after birth.  A total of 42 women and 43 children met the study criteria.  In total, 40 mothers and 6 unborn infants received 115 doses of CMV-HIG.  The treatment group (TG; CMV-DNA polymerase chain reaction-positive amniotic fluid) included 4 mothers; the multi-nomial group (MG; CMV-positive mother and unknown CMV status of fetus) included 38 mothers (39 infants).  For the 4 unborn infants in TG, CMV-HIG was administered either intra-umbilically or into the amniotic fluid; 3 of the 4 mothers received intravenous CMV-HIG.  Three children in TG remained CMV-positive and were asymptomatic at birth and during follow-up.  One infant in TG had symptomatic cCMV infection in-utero, at birth, and during follow-up.  In MG, 37 of 38 women received intravenous CMV-HIG and 2 of 39 infants received CMV-HIG in-utero.  In total, 9 (23.1 %) of 39 children in MG were positive for cCMV (including a terminated pregnancy).  All 8 instances of cCMV infection at birth in MG were asymptomatic at birth and during follow-up.  The fetus from the terminated pregnancy showed no sonographic symptoms of cCMV infection.  No severe side effect occurred in 115 CMV-HIG applications.  The authors concluded that CMV-HIG was well-tolerated.  Compared with published untreated mother-child pairs, the authors observed a trend toward a smaller risk for intrauterine CMV transmission following CMV-HIG application.  Signs of prenatal cCMV disease were not reversed after CMV-HIG.

Simioni et al (2013) stated that primary CMV infection during pregnancy is the leading infectious cause of congenital neurological disabilities.  Diagnosis of maternal primary CMV infection and fetal compromise can be difficult, as well as the fact that most infected child are asymptomatic at birth, which makes binomial CMV and pregnancy challenging.  The treatment of pregnant women with CMV-HIG has shown promising results.  However, as far as the authors knew, no randomized trials of immunoglobulin therapy of CMV-infected fetuses are ongoing. 

An UpToDate review on “Cytomegalovirus infection in pregnancy” (Sheffield and Boppana, 2013) states that “Hyperimmunoglobulin therapy of pregnant women with primary CMV infection in early pregnancy is a promising, but investigational, approach to reducing symptomatic infection in offspring.  Data are limited to the following studies …. There are several limitations to interpreting these data.  These include the lack of randomization, the absence of a control group that received placebo, the use of historic controls, a small number of adverse events, and use of interventions that differed in the therapy and prevention groups and in cases and controls.  None of the studies addressed the financial and logistical issues associated with screening large obstetrical populations for CMV infection and the expense of pursuing false positive results.  Until data from randomized trials are available, practitioners should emphasize the simple preventive measures noted below (see 'Prevention' below and 'Precautions to prevent transmission' below).  Although hyperimmunoglobulin therapy is not generally recommended, the use of this therapy should be individualized.  Some pregnant women with primary CMV infection may choose to undergo this therapy after a discussion of the available data on the efficacy of hyperimmunoglobulin and the limitations of the few published studies, as well as potential side effects of this therapy.  It is currently being evaluated in a large multicenter National Institutes of Health (NICHD) trial and the results of this trial will better guide recommendations.  A second randomized European trial has just been completed and final data are being analyzed”.

Hepatitis B Immune Globulin

Hepatitis B immune globulin is appropriate when used to provide passive immunization to hepatitis B as prophylaxis for certain exposed individuals.  The Advisory Committee on Immunization Practices (ACIP) states that combined passive and active immunization is preferred to passive immunization with HBIg alone in neonates born to HBsAb-positive women, in individuals exposed percutaneously or by ingestion or mucous membrane contact, and in individuals bitten by human carriers of HBsAG.  Also, combined treatment is recommended for patients exposed through sexual contact.  Hepatitis B immune globulin is administered promptly after exposure and again in 1 month.

Hepatitis B immune globulin is also indicated for prophylaxis of recurrent hepatitis B infection in HbsAg-positive liver transplant recipients.  Hepatitis B immune globulin prophylaxis is administered on a lifelong or indefinite basis for this indication.

The manufacturers state that the intra-muscular (IM) product is not to be used in an intravenous (IV0 fashion.  This is apparently because "serious systemic allergic reactions could occur following inadvertent IV administration of HBIg, since such reactions have occurred following IV administration of immune globulin".  Since it appears that the contraindication to IV use is theoretical, and that IV use is occurring without safety problems, it is appropriate to allow IV use when IM is not an option.

Rao and colleagues (2009) performed a systematic review and a meta-analysis to evaluate lamivudine monotherapy and combined therapy of lamivudine and HBIg in HBV infected liver recipients.  A fixed effects model was used for statistical pooling of relative risks (RR) for the different outcomes.  Six articles (n = 551) fulfilled the inclusion criteria.  Statistically significant differences were observed between lamivudine monotherapy and lamivudine + HBIg therapy in hepatitis B recurrence (p < 0.0001; RR = 0.38; 95 % confidence interval [CI]: 0.25 to 0.58), YMDD mutant (p = 0.002; RR = 0.40; 95 % CI: 0.23 to 0.72) and hepatitis B recurrence in HBV-DNA positive patients before orthotopic liver transplantation (p < 0.00001; RR = 0.31; 95 % CI: 0.21 to 0.45).  No significant differences were observed in patient survival (p = 0.59; RR = 1.02; 95 % CI: 0.95 to 1.09), graft survival (p = 0.56; RR = 1.02; 95 % CI: 0.95 to 1.09) and diseases leading to death between the 2 groups (HBV recurrence leading to death: p = 0.05; RR = 0.47; 95 % CI: 0.22 to 1.02); hepatocellular carcinoma recurrence leading to death: p = 0.13; RR = 0.34; 95 % CI: 0.09 to 1.36).  The authors concluded that combination of lamivudine and HBIg can effectively decrease the recurrence rate of HBV and the incidence of YMDD mutant, but it can not improve patient survival and graft survival significantly.  They stated that well-designed, large-sample trials are needed to evaluate the efficiency of combined therapy of lamivudine and HBIg in prophylaxis of HBV recurrence in liver graft recipients.

Hepatitis A Immune Globulin

Hepatitis A immune globulin is indicated for persons who are exposed or likely to be exposed to hepatitis A virus (HAV).  Risk groups include household and sexual contacts of persons with hepatitis A, newborn infants of HAV-infected mothers, staff and children at child-care centers and schools with HAV outbreaks, staff of custodial care institutions with HAV outbreaks, and individuals exposed to HAV through food or water-borne outbreaks.  The usual dose is a single IM injection administered within 2 weeks of exposure.

Rho-D Immune Globulin

Rhogam is a specially prepared immune globulin injected into an Rh-negative mother to prevent Rh hemolytic disease in future children.  Rho-D immune globulin may be indicated for prevention of Rh hemolytic disease in neonates by administration to selected pre-menopausal, Rho-D-negative females; and for treatment of selected Rho-D-positive patients with ITP.

Administration of Rhogam is recommended under generally accepted guidelines for all unsensitized Rh-negative women at 24 to 28 weeks gestation, unless the father is known to be Rh-negative.  If a Rh-positive infant is delivered, accepted guidelines indicate the dose should be repeated post-partum, preferably within 72 hours of delivery.  The American College of Obstetricians and Gynecologists recommends administration of Rhogam after other obstetric complications such as amniocentesis, chorionic villus sampling, ectopic pregnancy, pregnancy termination, cordocentesis, fetal surgery or manipulation (including external version), ante-partum placental hemorrhage, ante-partum fetal death, miscarriage and stillbirth.  The literature indicates this immune globulin may also be used for treatment of selected Rho-D-positive persons with idiopathic thrombocytopenic purpura.  Under generally accepted guidelines, Rhogam is recommended for all unsensitized Rh-negative women after elective abortion, unless the father is known to be Rh-negative.

WinRho may be administered intramuscularly or intravenously over 3 to 5 mins.  Other brands are indicated for IM use.  Intramuscular injection is a relative contraindication in patients with ITP; however, has been used with some success.  While some feel that use of this product for treatment of ITP may not be effective in splenectomized patients, others provide evidence to the contrary.  When given in conjunction with pregnancy, Rho-D immune globulin does not provide benefit for the infant from that pregnancy.  Its use is intended to prevent Rh hemolytic disease in future infants born to that mother.

Varicella Zoster Immune Globulin

Varicella zoster immune globulin (VZIG) is considered appropriate when used to prevent varicella (chickenpox) infection as recommended by the ACIP.  According to the ACIP, VZIG is necessary, provided that significant exposure has occurred for immunocompromised children without a history of chickenpox.  Immuocompromised adolescents and adults are likely to be immune, but if susceptible, should also receive VZIG.  Varicella zoster immune globulin is also necessary, provided that significant exposure has occurred, for the following groups; susceptible pregnant women; newborn infants whose mother had onset of chickenpox within the 5 days before delivery or within the 48 hours after delivery; hospitalized premature infants (greater than or equal to 28 weeks gestation) whose mother has no history of chickenpox; and hospitalized premature infants (less than 28 weeks of gestation or less than or equal to 1,000 grams) regardless of maternal history.

Varicella zoster immune globulin may be indicated in the above listed susceptible groups if significant exposure to varicella has occurred in the hospital: in the same 2- to 4-bed room, or adjacent beds in a large ward; face-to-face contact with an infectious staff memeber or patient, or visit by a person deemed contageous.  Experts differ in the duration of face-to-face contact that warrants the administration of VZIG.  Some experts suggest a contact of 5 or more mins as constituting significant exposure for this purpose; others define close contact as more than 1 hour.  In any case, the face-to-face contact should be non-transient to be considered significant.

Other types of exposure for which VZIG is indicated in the above listed susceptible groups include: household exposure (residing in the same household); exposure from playmates (face-to-face indoor play); and intimate contact with zoster lesions (e.g., touching or hugging a person deemed contageous; and exposure of newborn infant (onset of varicella in the mother 5 days or less before delivery or within 48 hours after delivery; VZIG is not indicated if the mother has zoster).  The ACIP recommends that VZIG be administered within 96 hours of exposure

Laboratory determination of susceptibility to varicella is sometimes impractical.  Because of this, the ACIP recommends that determination of susceptibility be based on a carefully obtained history of prior infection or exposure.  However, in the case of pregnant women, serologic status should be determined through immunofluorescent assay or ELISA test if results can be available within 96 hours of exposure.  If this test is feasible and negative, immune globulin need not be given.  Otherwise, pregnant women should be considered susceptible.

Varicella zoster immune globulin is not necessary in individuals who are considered to be immune to varicella zoster.  With the exception of bone marrow transplant recipients, individuals considered to be immune to varicella zoster include those with a history of prior varicella infection, or negative or uncertain exposure if they are at least 15 years of age and immunocompetent.  In addition, patients with a history of infection with varicella or herpes zoster subsequent to bone marrow transplant are considered to be immune.

There is currently no evidence that administration of VZIG to pregnant women during the first or second trimester of pregnancy will prevent congenital varicella syndrome or that administration during the third trimester will prevent neonatal varicella.  In addition, post-exposure administration of VZIG in susceptible, pregnant women may prevent or suppress clinical disease in the mother without preventing fetal infection or disease.  For this reason, administration of VZIG for pregnant women who do not fit the criteria listed above is not considered to be necessary.

VariZIG (Cangene Corporation, Winnipeg, Canada) is the only VZIG preparation available in the United States for post-exposure prophylaxis of varicella in persons at high-risk for severe disease who lack evidence of immunity to varicella and are ineligible for varicella vaccine.  VariZIG is available in the United States through an investigational new drug (IND) application expanded access protocol.  It is a purified immune globulin preparation made from human plasma containing high levels of anti-varicella zoster virus antibodies (immunoglobulin G).  In May 2011, the FDA approved an extended period for administering VariZIG.  The period after exposure to varicella zoster virus during which a patient may receive VariZIG, which had been 96 hours (4 days), is now 10 days.  VariZIG should be administered as soon as possible after exposure (CDC, 2012).

Vaccinia (Smallpox) Immune Globulin

Vaccinia vaccine is indicated for treatment of vaccine complications with severe clinical manifestations (e.g., eczema vaccinatum, progressive vaccinia, severe generalized vaccinia, and severe ocular viral implantation).  The only product currently available for treatment of complications of vaccinia vaccination is vaccinia immunoglobulin, which is an isotonic sterile solution of the immunoglobulin fraction of plasma from persons vaccinated with vaccinia vaccine.  It is effective for treatment of eczema vaccinatum and certain cases of progressive vaccinia; it might be useful also in the treatment of ocular vaccinia resulting from inadvertent implantation.  However, vaccinia immunoglobulin is contraindicated for the treatment of vaccinial keratitis.  Vaccinia immunoglobulin is recommended for severe generalized vaccinia if the individual is extremely ill or has a serious underlying disease.  Vaccinia immunoglobulin provides no benefit in the treatment of post-vaccinial encephalitis and has no role in the treatment of smallpox.  The Centers for Disease Control and Prevention (CDC) (2001) states that current supplies of vaccinia immunoglobulin are limited, and its use should be reserved for treatment of vaccine complications with serious clinical manifestations.  According to the CDC (2001), vaccinia immunoglobulin should be administered as early as possible after the onset of symptoms.  Doses can be repeated, usually at intervals of 2 to 3 days, until recovery begins (e.g., no new lesions appear).  The CDC is currently the only source of vaccinia immunoglobulin for civilians.

Rabies Immue Globulin

Rabies immune globulin is indicated for treatment of rabies exposure where the animal has escaped or is known to be rabid at the time of direct exposure or attack.  Treatment of rabies exposure is comprised of a series of rabies vaccine (human diploid cell vaccine, HDCV) and a single rabies immune globulin injection (Rabies Immune Globulin, RIG).  For persons not previously vaccinated with HDCV, the usual frequency is a single IM injection of RIG and a series of HDCV consisting of 1-ml IM injection in the deltoid area on days 0, 3, 7, and 14.  For persons previously vaccinated with HDCV, 2 HDCV IM injections are given on days 0 and 3.  The literature indicates rabies immune globulin should not be administered to previously vaccinated individuals.

Tetanus Immune Globulin

Intramuscular injection of tetanus immune gamma globulin are indicated for prevention of tetanus in immunized or non-immunized persons for neglected or tetanus-prone wounds (contaminated, necrotizing, or puncture wounds).  Post-exposure prophylaxis with tetanus toxoid is recommended under accepted guidelines for wounded persons who have not completed the 3-dose primary vaccination series, and those who have completed vaccination more than 10 years ago.  In addition, accepted guidelines state incompletely vaccinated persons with serious or contaminated wounds should receive human tetanus immune globulin.  The usual dose is a single IM injection repeated at 4-week intervals, if necessary.

Rubeola (Measles) Immune Globulin

Intramuscular injection of measles (rubeola) immune globulin is indicated for unvaccinated individuals exposed to the disease.  Accepted guidelines recommend that the immune globulin should be administered within 6 days of exposure.

Immune Globulin for Rubella (German Measles)

The use of immune globulin for pregnant women with acute infection is controversial.  There are no data to suggest that immune globulin will have any beneficial effect on the fetal response to disease.  Thus, the CDC recommends limiting the use of immune globulin to women with known rubella exposure who decline pregnancy termination.  The usual dose of immune globulin is a single IM injection.

Infantile Botulism Immune Globulin

Arnon et al (2006) created the orphan drug Human Botulism Immune Globulin Intravenous (Human) (BIG-IV), which neutralizes botulinum toxin, and evaluated its safety and efficacy in treating infant botulism, the intestinal-toxemia form of human botulism.  These investigators performed a 5-year, randomized, double-blind, placebo-controlled trial statewide, in California, of BIG-IV in 122 infants with suspected (and subsequently laboratory-confirmed) infant botulism (75 caused by type A Clostridium botulinum toxin, and 47 by type B toxin); treatment was given within 3 days after hospital admission.  These researchers subsequently performed a 6-year nationwide, open-label study of 382 laboratory-confirmed cases of infant botulism treated within 18 days after hospital admission.  As compared with the control group in the randomized trial, infants treated with BIG-IV had a reduction in the mean length of the hospital stay, the primary efficacy outcome measure, from 5.7 weeks to 2.6 weeks (p < 0.001).  BIG-IV treatment also reduced the mean duration of intensive care by 3.2 weeks (p < 0.001), the mean duration of mechanical ventilation by 2.6 weeks (p = 0.01), the mean duration of tube or intravenous feeding by 6.4 weeks (p < 0.001), and the mean hospital charges per patient by 88,600 dollars (in 2004 U.S. dollars; p < 0.001).  There were no serious adverse events attributable to BIG-IV.  In the open-label study, infants treated with BIG-IV within 7 days of admission had a mean length of hospital stay of 2.2 weeks, and early treatment with BIG-IV shortened the mean length of stay significantly more than did later treatment.  The authors concluded that prompt treatment of infant botulism type A or type B with BIG-IV was safe and effective in shortening the length and cost of the hospital stay and the severity of illness.

Underwood et al (2007) reported a tertiary care hospital's 30-year experience with the diagnosis, treatment, and outcome of infant botulism in the PICU before and after the availability of Botulism Immune Globulin Intravenous.  This was a retrospective medical chart review of the 67 patients who had received a diagnosis of infant botulism and were admitted to the ICU from 1976 to 2005.  The ages on presentation, length of hospital stay, length of ICU stay, length of mechanical ventilation, and type of botulism toxin were recorded and compared for patients who had received Botulism Immune Globulin Intravenous and those who had not.  On the basis of these results, conclusions were drawn regarding the effect of Botulism Immune Globulin Intravenous on the morbidity of infant botulism.  A total of 67 patients' charts were reviewed; 23 male and 29 female patients did not receive Botulism Immune Globulin Intravenous.  Of patients who did not receive Botulism Immune Globulin Intravenous, the median age at presentation was 71 days, median length of hospital stay was 35 days, ICU stay was 24 days, and duration of mechanical ventilation was 17 days.  A total of 40 % had type A toxin, and 60 % had type B toxin.  There was a significant difference between patients with toxin types A and B in length of hospital stay but not length of ICU stay or mechanical ventilation.  Patients with type A toxin were significantly older than patients with type B toxin.  Fifteen children received Botulism Immune Globulin Intravenous.  There were statistically significant differences in length of hospital stay, length of ICU stay, and length of mechanical ventilation between patients who received Botulism Immune Globulin Intravenous and those who did not.  The authors concluded that the use of Botulism Immune Globulin Intravenous significantly decreased the length of ICU stay, length of mechanical ventilation, and overall hospital stay in children with infant botulism.

Vanella de Cuetos et al (2011) stated that infant botulism is the most common form of human botulism in Argentina and the United States.  BabyBIG (botulism immune globulin intravenous [human]) is the antitoxin of choice for specific treatment of infant botulism in the United States.  However, its high cost limits its use in many countries.  These investigators reported the effectiveness and safety of equine botulinum antitoxin (EqBA) as an alternative treatment.  They conducted an analytical, observational, retrospective, and longitudinal study on cases of infant botulism registered in Mendoza, Argentina, from 1993 to 2007.  They analyzed 92 medical records of laboratory-confirmed cases and evaluated the safety and efficacy of treatment with EqBA.  Forty-nine laboratory-confirmed cases of infant botulism demanding admission in ICUs and mechanical ventilation included 31 treated with EqBA within the 5 days after the onset of signs and 18 untreated with EqBA.  EqBA-treated patients had a reduction in the mean length of hospital stay of 23.9 days (p = 0.0007).  For infants treated with EqBA, the ICU stay was shortened by 11.2 days (p = 0.0036), mechanical ventilation was reduced by 11.1 days (p = 0.0155), and tube feeding was reduced by 24.4 days (p = 0.0001).  The incidence of sepsis in EqBA-treated patients was 47.3 % lower (p = 0.0017) than in the untreated ones.  Neither sequelae nor adverse effects attributable to EqBA were noticed, except for 1 infant who developed a transient erythematous rash.  The authors concluded that these results suggested that prompt treatment of infant botulism with EqBA is safe and effective and that EqBA could be considered an alternative specific treatment for infant botulism when BabyBIG is not available.

Also, an UpToDate review on “Botulism” (Pegram and Stone, 2012) states that “Human-derived botulinum immune globulin -- Human-derived botulinum immune globulin (called BIG-IV or BabyBIG) is available for intravenous use in infants less than one year of age who are diagnosed with infant botulism.  BIG-IV should be administered as early as possible in the illness”.

BabyBIG, botulism immune globulin intravenous (human) (BIG-IV), is an orphan drug that consists of human-derived botulism antitoxin antibodies that is approved by the FDA for the treatment of infant botulism types A and B.

BabyBIG is given as a single IV infusion.  Recommended dose is 1.5 mL/kg (75 mg/kg) given as a single intravenous infusion.  Begin infusion slowly (0.5 mL/kg/h); if no untoward reaction in 15 minutes, increase rate to 1.0 mL/kg/h (2.2, 2.3).  (At the recommended rates, infusion of the indicated dose should take 97.5 minutes total elapsed time).    http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm117160.pdf.