Adverse events at least possibly causally related to palivizumab (ADRs) are displayed by system organ class and frequency (very common: ≥ 1/10; common: ≥ 1/100 to < 1/10; uncommon: ≥ 1/1000 to < 1/100; rare: ≥ 1/10000 to < 1/1000) in studies conducted in premature and bronchopulmonary dysplasia patients and pediatric congenital heart disease patients (table).
Adverse drug reactions (ADRs) reported in the prophylactic pediatric studies were similar in the placebo and palivizumab groups. The majority of ADRs were transient and mild to moderate in severity.
IMpact-RSV Study: In the study of premature infants and children with bronchopulmonary dysplasia, no medically important differences in ADRs by body system or in subgroups of children categorized by gender, age, gestational age, country, race/ethnicity or quartile serum palivizumab concentration were observed. No significant difference in safety profile was observed between children without active RSV infection and those hospitalised for RSV. Permanent discontinuation of palivizumab because of ADRs was rare (0.2%). Deaths were balanced between the placebo and palivizumab treatment groups and were not drug-related.
CHD Study: In the congenital heart disease study, no medically important differences were observed in ADRs by body system or when evaluated in subgroups of children by cardiac category (cyanotic versus acyanotic). The incidence of serious adverse events was significantly lower in the palivizumab group, as compared to the placebo group. No serious adverse events related to palivizumab were reported. The incidences of cardiac surgeries classified as planned, earlier than planned, or urgent, were balanced between the groups. Deaths associated with RSV infection occurred in 2 patients in the palivizumab group and 4 patients in the placebo group and were not drug-related. (See table.)
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Extended Dose Study: No reported adverse events were considered related to palivizumab and no deaths were reported in this study.
Immunogenicity: In the IMpact-RSV trial, the incidence of anti-palivizumab antibody following the fourth injection was 1.1% in the placebo group and 0.7% in the palivizumab group. In pediatric patients receiving palivizumab for a second season, one of the fifty-six patients had transient, low titer reactivity. This reactivity was not associated with adverse events or alteration in palivizumab serum concentrations. Immunogenicity was not assessed in the CHD Study.
Antibody to palivizumab was also evaluated in four additional studies in 4337 palivizumab-treated patients (children born at 35 weeks of gestation or less and 6 months of age or less, or < 24 months of age with bronchopulmonary dysplasia or with haemodynamically significant congenital heart disease were included in these studies) and was observed in 0% - 1.5% of patients at different study time points. There was no association observed between the presence of antibody and adverse events. Therefore, anti-drug antibody (ADA) responses appear to be of no clinical relevance.
In the Extended Dose Study, transient, low levels of anti-palivizumab antibody were observed in one child after the second dose of palivizumab that dropped to undetectable levels at the fifth and seventh dose.
Post-marketing Experience: The following adverse reactions have been reported with palivizumab therapy. 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 palivizumab exposure (see also PRECAUTIONS).
Blood and the lymphatic system disorders: Thrombocytopenia.
Immune system disorders: Anaphylaxis, anaphylactic shock (In some cases, fatalities have been reported).
Nervous system disorders: Convulsion.
Skin and subcutaneous tissue disorders: Urticaria.
Palivizumab treatment schedule and adverse events were monitored in a group of nearly 20,000 infants tracked through a patient compliance registry, the REACH program. Of this group, 1250 enrolled infants received 6 injections, 183 infants received 7 injections, and 27 infants received either 8 or 9 injections, each respectively. Adverse events observed in patients following a sixth or greater dose from this registry as well as through routine post marketing surveillance were similar in character and frequency to those after the initial 5 doses.