in-Barré syndrome), cerebrovascular accident
Respiratory disorders: Interstitial lung disease, including pulmonary fibrosis, pulmonary embolism
Skin reactions: Stevens Johnson Syndrome, cutaneous vasculitis, erythema multiforme, new or worsening psoriasis (all sub-types including pustular and palmoplantar), alopecia
Vascular disorders: Systemic vasculitis, deep vein thrombosis
Drug Interactions
Methotrexate
Humira has been studied in rheumatoid arthritis (RA) patients taking concomitant methotrexate (MTX). Although MTX reduced the apparent adalimumab clearance, the data do not suggest the need for dose adjustment of either Humira or MTX [see Clinical Pharmacology (12.3)].
Biological Products
In clinical studies in patients with RA, an increased risk of serious infections has been seen with the combination of TNF blockers with anakinra or abatacept, with no added benefit; therefore, use of Humira with abatacept or anakinra is not recommended in patients with RA [see Warnings and Precautions (5.7 and 5.11)]. A higher rate of serious infections has also been observed in patients with RA treated with rituximab who received subsequent treatment with a TNF blocker. There is insufficient information regarding the concomitant use of Humira and other biologic products for the treatment of RA, PsA, AS, CD, UC, and Ps. Concomitant administration of Humira with other biologic DMARDS (e.g., anakinra and abatacept) or other TNF blockers is not recommended based upon the possible increased risk for infections and other potential pharmacological interactions.
Live Vaccines
Avoid the use of live vaccines with Humira [see Warnings and Precautions (5.10)].
Cytochrome P450 Substrates
The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (e.g., TNFα, IL-6) during chronic inflammation. It is possible for a molecule that antagonizes cytokine activity, such as adalimumab, to influence the formation of CYP450 enzymes. Upon initiation or discontinuation of Humira in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category B
Risk Summary
Adequate and well controlled studies with Humira have not been conducted in pregnant women. Adalimumab is an IgG1 monoclonal antibody and IgG1 is actively transferred across the placenta during the third trimester of pregnancy. Adalimumab serum levels were obtained from ten women treated with Humira during pregnancy and eight newborn infants suggest active placental transfer of adalimumab. No fetal harm was observed in reproductive studies performed in cynomolgus monkeys. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Clinical Considerations
In general, monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester.
Human Data
In an independent clinical study conducted in ten pregnant women with inflammatory bowel disease treated with Humira, adalimumab concentrations were measured in maternal blood as well as in cord (n=10) and infant blood (n=8) on the |
