ials, although not in multicentric Castleman's disease (MCD) trials. Use caution in patients who may be at increased risk of GI perforation.
Pregnancy
Siltuximab is pregnancy risk category C. The FDA-labeling suggests that use during pregnancy should be weighed against the potential risk to the fetus. There are no adequate or well-controlled studies in pregnant women. Animal studies suggest siltuximab may cross the placenta. Babies born to pregnant women treated with siltuximab may be at increased risk of infection and caution is advised in the administration of live vaccines to these babies. Patients of childbearing potential should avoid pregnancy and women of childbearing potential should use contraception during use and for the 3 months after treatment.
Breast-feeding
FDA-labeling states that it is not known whether siltuximab is excreted in human milk or is absorbed systemically after ingestion. However, because many immunoglobulins are excreted in human milk and due to the potential for adverse reactions in the nursing baby, the manufacturer recommends that a decision be made whether to discontinue nursing or to discontinue siltuximab. Consider the benefits of breast-feeding, the risk of infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
Children, infants, neonates
Infants born to pregnant women treated with siltuximab may be at increased risk of infection and caution is advised in the administration of live vaccines to these infants. Safe and effective use of siltuximab has not been established in neonates, infants, children, and adolescents.
ADVERSE REACTIONS
Severe
eczema vaccinatum / Delayed / 4.0-4.0
anaphylactoid reactions / Rapid / 0-1.0
GI perforation / Delayed / Incidence not known
Moderate
edema / Delayed / 26.0-26.0
peripheral edema / Delayed / 16.0-16.0
hyperuricemia / Delayed / 11.0-11.0
thrombocytopenia / Delayed / 9.0-9.0
constipation / Delayed / 8.0-8.0
hypertriglyceridemia / Delayed / 8.0-8.0
hypotension / Rapid / 4.0-6.0
infusion-related reactions / Rapid / 4.8-4.8
psoriasis / Delayed / 4.0-4.0
hypercholesterolemia / Delayed / 4.0-4.0
dehydration / Delayed / 4.0-4.0
antibody formation / Delayed / 0.2-0.2
Mild
infection / Delayed / 8.0-63.0
diarrhea / Early / 32.0-32.0
pruritus / Rapid / 28.0-28.0
rash (unspecified) / Early / 28.0-28.0
maculopapular rash / Early / 28.0-28.0
fatigue / Early / 21.0-21.0
arthralgia / Delayed / 21.0-21.0
weight gain / Delayed / 19.0-19.0
abdominal pain / Early / 12.0-12.0
headache / Early / 8.0-8.0
xerosis / Delayed / 4.0-4.0
skin hyperpigmentation / Delayed / 4.0-4.0
DRUG INTERACTIONS
Amlodipine; Atorvastatin: Caution is warranted in patients with co-administered CYP3A4 substrates, such as atorvastatin, in which a decreased effect would be undesirable. Cytochrome P450s in the liver are down regulated by infection and inflammation stimuli, including cytokines such as interleukin-6 (IL-6). Inhibition of IL-6 signaling by siltuximab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. The effect of siltuximab on CYP450 enzyme activity can persist for several weeks after stopping therapy.
Atorvastatin |
