During post marketing surveillance, very rare cases of anaphylactic shock (< 1 case per 100,000 patients) have been reported after re-exposure to palivizumab [44346]; some cases have been fatal.[42668] Rare acute anaphylactoid reactions have also been reported on initial exposure or re-exposure to palivizumab. Hypersensitivity reactions may include dyspnea, decreased oxygenation, respiratory failure, urticaria, pruritus, angioedema, hypotonia, and unresponsiveness. The relationship between these reactions and the development of antibodies to palivizumab is unknown. If hypotension, anaphylaxis, or a severe allergic reaction occurs, palivizumab should be permanently discontinued. Epinephrine and supportive care should be administered as necessary.[42668] Skin rash (unspecified) has been reported in patients receiving palivizumab in clinical trials. In one study of high-risk infants, rash occurred in 0.9% of patients receiving palivizumab (n = 1002) and 0.2% of patients receiving placebo (n = 500).[25419] Two additional clinical trials reported rash in 12% of patients receiving palivizumab (n = 1639) versus 10% of patients receiving placebo (n = 1143).[49668]

Injection site reactions may be observed in patients who receive IM administration of palivizumab. In one study of high-risk infants (n = 1002 in palivizumab group), 2.3% of patients who received palivizumab experienced an injection site reaction. These reactions included erythema (1.4% palivizumab vs. 1.2% placebo), pain (0.6% palivizumab vs. 0 placebo), induration/swelling (0.6% palivizumab vs 0.2% placebo), and bruising (0.3% palivizumab vs. 0.4% placebo).[25419]

Elevated hepatic enzymes were reported in clinical trials of palivizumab. In all cases these elevations were mild or moderate. Of 1641 patients ages 3 days to 24 months who received palivizumab, 3% experienced an increase in AST compared to 1.7% of those who received placebo (n = 1148).[42668] In one study of high-risk infants (n = 1002 in the palivizumab group), elevations in AST occurred in 3.6% of palivizumab treated children, and 1.6% of placebo recipients, respectively. ALT elevations occurred in 2.3% of palivizumab recipients versus 2% of controls. Hepatic and renal adverse events thought to be related to study participation occurred in similar percentages in both groups as judged by a blinded investigator.[25419]

Upper respiratory tract infection, otitis media, and fever were the most commonly observed adverse events during palivizumab clinical trials; however, because palivizumab is often studied in infants and young children at high risk for respiratory infections, it is difficult to determine what portion of these events were related to palivizumab therapy and what portion represented background incidences. In clinical trials, there was a slightly higher incidence of upper respiratory infection (50.6% vs. 47.4%), otitis media (36.4% vs. 34.6%), fever (27.1% vs. 25.2%), and rhinitis (26.8% vs. 24.6) in palivizumab-treated patients (n = 1641) compared to those who received placebo (n = 1148). Other adverse events reported in relation to palivizumab administration include cough and wheezing.[42668]

Gastrointestinal side effects of palivizumab are rare and comparable to rates seen with placebo. Hernia was reported in 4.1% of patients receiving palivizumab versus 2.6% of those patients receiving placebo. Other gastrointestinal adverse events reported in relation to palivizumab administration include diarrhea, vomiting, and gastroenteritis.[42668]

In clinical trials with palivizumab lyophilized formulation, the incidence of antibody formation, specifically, anti-humanized antibody, was 0.7% in the palivizumab-treated group after the fourth monthly dose. In patients receiving palivizumab for a second season, 1 of 56 patients had transient, low-titer reactivity. The development of the antibody was not associated with adverse events or alterations in palivizumab activity in the first season of use. In addition, the possibility exists that the liquid solution may be more immunogenic than the lyophilized formulation. Anti-palivizumab antibodies were found in one patient who received the lyophilized formulation verses no patients receiving the liquid formulation in a clinical trial of 379 high-risk preterm children < = 24 months of age. Antibodies in this study were detected using an enzyme-linked immunosorbent assay (ELISA), which has limitations in detecting anti-palivizumab antibodies in the presence of palivizumab. Rates of anti-palivizumab antibodies were assessed in 2 additional clinical trials using an electrochemical luminescence (ECL) based immunogenicity assay and were found to be 1.1% and 1.5%.[49668]

Post-marketing reports of adverse events associated with the use of palivizumab have included reports of severe thrombocytopenia (platelet count < 50,000/microliter). A causal relationship to palivizumab exposure has not been established.[42668]

In a clinical trial of pediatric patients < = 24 months of age with congenital heart disease who received palivizumab prophylaxis, cyanosis occurred in 9.1% of patients and arrhythmias or arrhythmia exacerbation occurred in 3.1% of patients compared to 6.9% and 1.7% of patients receiving placebo, respectively.[42668]

Palivizumab should be given as an intramuscular injection (IM). Caution should be used when administering IM injections to patients with thrombocytopenia or other bleeding disorders, or coagulopathy. Palivizumab may be used in such individuals with caution if the potential benefits outweigh the risk of administration. Vaccination of adult populations with palivizumab is not recommended at this time.

Palivizumab is contraindicated in patients with a history of a severe prior reaction to palivizumab or to other components of this product. Palivizumab is a composite of human and murine antibody sequences and may be inappropriate for use by patients with known murine protein hypersensitivity. With any biologic product, the prescriber or health care professional should take precautions to prevent allergic reactions. Very rare cases of anaphylaxis have been reported (see Adverse Reactions). If hypotension, acute bronchospasm, anaphylaxis, or a severe allergic reaction occurs, palivizumab should be permanently discontinued. Epinephrine and supportive care should be administered as necessary. If a milder hypersensitivity reaction occurs, caution should be used on readministration of palivizumab. The health care professional should have immediate availability of epinephrine (1:1000) injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction to palivizumab.

Studies indicate a low level of immunogenicity of palivizumab. Patients who develop human anti-human antibody (HAHA) titers may have allergic or hypersensitivity reactions when treated with palivizumab or other humanized monoclonal antibodies. In clinical trials with palivizumab, the incidence of anti-humanized antibody was 0.7% in the palivizumab treated group after the fourth monthly dose. The development of the antibody was not associated with adverse events or alterations in palivizumab activity in the first season of use. Anti-palivizumab antibodies were found in one patient who received the lyophilized formulation verses no patients receiving the liquid formulation in a clinical trial of 379 high-risk preterm children <= 24 months of age. Antibodies in this study were detected using an enzyme-linked immunosorbent assay (ELISA) which has limitations in detecting anti-palivizumab antibodies in the presence of palivizumab. Rates of anti-palivizumab antibodies were assessed in 2 additional clinical trials using an electrochemical luminescence (ECL) based immunogenicity assay and were found to be 1.1% and 1.5%.[49668]

Palivizumab has been classified as FDA pregnancy risk category C. Studies in animal or human reproduction have not been conducted. It is unknown if palivizumab can cause fetal harm or affect reproductive capacity.[42668]

Palivizumab is not approved for use in women of childbearing age and data regarding its' administration during breast-feeding is unavailable. The manufacturer does not state whether the drug is excreted in human milk.[42668]

Serum concentrations of palivizumab are significantly decreased after cardio-pulmonary bypass. Patients who undergo surgery involving cardio-pulmonary bypass or who undergo extracorporeal membrane oxygenation (ECMO) should receive a dose of palivizumab as soon as possible after the procedure or at the conclusion of ECMO, even if it has been less than a month since their last dose.[42668] [57698]