Patients treated with adalimumab are at increased risk of developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants, such as methotrexate or corticosteroids.
Discontinue adalimumab if a patient develops a serious infection or sepsis. Reported infections include the following:
Active tuberculosis (TB), including reactivation of latent TB. Patients with TB frequently have presented with disseminated or extrapulmonary disease. Test patients for latent TB before adalimumab use and during therapy. Initiate treatment for latent infection prior to adalimumab use.
Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric antifungal therapy in patients at risk of invasive fungal infections who develop severe systemic illness.
Bacterial, viral, and other infections caused by opportunistic pathogens, including Legionella and Listeria.
Carefully consider the risks and benefits of treatment with adalimumab prior to initiating therapy in patients with chronic or recurrent infection.
Monitor patients closely for the development of signs and symptoms of infection during and after treatment with adalimumab, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.
Lymphoma and other malignancies, some fatal, have been reported in children and adolescents treated with tumor necrosis factor (TNF)–blockers, including adalimumab. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF-blockers, including adalimumab. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF-blocker cases have occurred in patients with Crohn disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF-blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF-blocker or a TNF-blocker in combination with these other immunosuppressants.
Dosage guidance:
Safety: Before therapy initiation, ensure appropriate immunization (if possible) and screen for active or latent infections. Treatment of tuberculosis (TB) infection (latent TB) is required before starting adalimumab. Avoid use in patients with severe active infections (Ref).
Dosage form information: In the United States, Abrilada (adalimumab-afzb), Amjevita (adalimumab-atto), Cyltezo (adalimumab-adbm), Hadlima (adalimumab-bwwd), Hulio (adalimumab-fkjp), Hyrimoz (adalimumab-adaz), Idacio (adalimumab-aacf), Yuflyma (adalimumab-aaty), and Yusimry (adalimumab-aqvh) have been approved as biosimilars to Humira (adalimumab). In Canada, Abrilada, Amgevita, Hadlima, Hulio, Hyrimoz, Idacio, Simlandi, and Yuflyma are also approved as biosimilars to Humira; refer to Canadian product monograph(s) for biosimilar-specific indication details.
Axial spondyloarthritis, including ankylosing spondylitis (Humira and adalimumab biosimilars):
Note: Reserve for patients who do not have an adequate response to nonsteroidal anti-inflammatory drugs (NSAIDs); may continue NSAIDs and/or analgesics (Ref).
SUBQ: 40 mg every other week.
Crohn disease, moderate to severe, induction and maintenance of remission (Humira and adalimumab biosimilars):
Note: Combination therapy with an immunomodulator (ie, thiopurine or methotrexate) is generally preferred (Ref).
Initial: SUBQ: 160 mg (given over 1 or 2 days), then 80 mg 2 weeks later (day 15). Note: If switching from another anti-tumor necrosis factor agent, may use this induction regimen.
Maintenance: SUBQ: 40 mg every other week beginning day 29.
Hidradenitis suppurativa, moderate to severe, refractory (Humira and adalimumab biosimilars):
Initial: SUBQ: 160 mg (given over 1 or 2 days), then 80 mg 2 weeks later (day 15).
Maintenance: SUBQ: 40 mg every week beginning day 29 or 80 mg every other week beginning day 29 (Ref). Note: 40 mg every week regimen has been more extensively studied and is therefore preferred by some experts (Ref).
Nonradiographic axial spondyloarthritis (off-label use):
Note: Reserve for patients who do not have an adequate response to NSAIDs; may continue NSAIDs and/or analgesics (Ref).
SUBQ: 40 mg every other week.
Plaque psoriasis, moderate to severe (Humira and adalimumab biosimilars):
Note: Generally used as systemic monotherapy; may continue adjuvant topical therapies (eg, emollients, corticosteroids) as needed. A clinician experienced with use of adalimumab for plaque psoriasis should be involved in treatment.
Initial: SUBQ: 80 mg as a single dose.
Maintenance: SUBQ: 40 mg every other week beginning 1 week after initial dose. Note: Some patients may require 40 mg every week (Ref).
Psoriatic arthritis (Humira and adalimumab biosimilars):
Note: May continue methotrexate, other nonbiologic DMARDs, corticosteroids, NSAIDs, and/or analgesics.
SUBQ: 40 mg every other week.
Rheumatoid arthritis (Humira and adalimumab biosimilars):
Note: For use as an alternative to methotrexate in disease-modifying antirheumatic drug (DMARD)–naive patients with moderate to high disease activity, or as adjunctive therapy in patients who have not met treatment goals despite maximally tolerated methotrexate therapy (Ref). May use in combination with other nonbiologic DMARDs, glucocorticoids, NSAIDs, and/or analgesics. A clinician experienced with use of adalimumab for rheumatoid arthritis should be involved in treatment.
SUBQ: Initial: 40 mg every other week; for select patients with an inadequate response, may increase dose to 40 mg every week or 80 mg every other week.
Sarcoidosis, refractory (adjunctive agent) (off-label use):
Note: For use as an adjunctive agent in patients in whom treatment goals have not been met despite glucocorticoids and other immunosuppressants (eg, methotrexate) (Ref). A clinician experienced with use of adalimumab should be involved in treatment.
Initial: SUBQ: The optimal dosing strategy is not known; one example of an initial regimen is 40 to 120 mg on week 0, 40 to 80 mg on week 1, and 40 mg on week 2 (Ref).
Maintenance: SUBQ: 40 mg every 1 to 2 weeks (Ref). The optimal frequency and duration of therapy are not known and must be individualized based on response; after a stable response is achieved (eg, after 6 months), one option is to gradually prolong the dosing interval (eg, to every 2 weeks) and discontinue after 3 months if response remains adequate (Ref).
Ulcerative colitis, moderate to severe, induction and maintenance of remission (Humira and adalimumab biosimilars):
Initial: SUBQ: 160 mg (given over 1 or 2 days), then 80 mg 2 weeks later (day 15).
Maintenance: SUBQ: 40 mg every other week beginning day 29. If a disease flare occurs, some experts increase to 40 mg every week (Ref). Note: Only continue maintenance treatment in patients demonstrating clinical remission by 8 weeks (day 57) of therapy.
Uveitis, noninfectious (Humira and adalimumab biosimilars [except Yuflyma]):
Note: Generally reserved for patients with an incomplete response to first-line agents and ≥1 other systemic therapies (Ref).
Initial: SUBQ: 80 mg as a single dose.
Maintenance: SUBQ: 40 mg every other week beginning 1 week after initial dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Theoretically, adalimumab’s large molecular weight (148,000 daltons) precludes the drug from being efficiently filtered at the glomerulus or by dialysis filters; hence, dose adjustments for kidney dysfunction and/or renal replacement therapies should generally be unnecessary (Ref).
Altered kidney function: SUBQ : No dosage adjustment necessary for any degree of kidney dysfunction (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m 2 ): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref): SUBQ : No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzed (Ref): SUBQ : No dosage adjustment or supplemental dose necessary; patients with end-stage kidney disease (ESKD) often suffer from impaired immune function, monitor closely for infection during adalimumab therapy (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzed (Ref): SUBQ : No dosage adjustment necessary; patients with ESKD often suffer from impaired immune function; monitor closely for infection during adalimumab therapy (Ref).
CRRT: SUBQ : No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): SUBQ : No dosage adjustment necessary (Ref).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
(For additional information see "Adalimumab (including biosimilars): Pediatric drug information")
Dosage guidance:
Dosage form information: In the United States, Amjevita (adalimumab-atto) has been approved as a biosimilar to Humira (adalimumab). In Canada, Abrilada, Amgevita, Hadlima, Hulio, Hyrimoz, Idacio, Simlandi, and Yuflyma are also approved as biosimilars to Humira; refer to Canadian product monograph(s) for biosimilar-specific indication details. Approved ages and uses may vary (consult product labeling).
Crohn disease, moderate to severe:
Children ≥6 years and Adolescents:
17 kg to <40 kg: SUBQ:
Initial: 80 mg on day 1, then 40 mg administered 2 weeks later (day 15).
Maintenance (beginning day 29): 20 mg every other week (Ref). Patients who continue to experience flares after 12 weeks of therapy may benefit from weekly dosing (Ref).
≥40 kg: SUBQ:
Initial: 160 mg (administered on day 1 or split and administered over 2 consecutive days), then 80 mg administered 2 weeks later (day 15).
Maintenance (beginning day 29): 40 mg every other week (Ref). Weekly dosing should be considered for patients with loss of response or low trough concentrations (<7.5 mcg/mL) (Ref).
Hidradenitis suppurativa:
Children ≥12 years and Adolescents:
30 to <60 kg: SUBQ:
Initial: 80 mg on day 1.
Maintenance (beginning day 8): 40 mg every other week.
≥60 kg: SUBQ:
Initial: 160 mg (administered as full dose on day 1 or dose split and administered over 2 consecutive days), then 80 mg 2 weeks later (day 15).
Maintenance (beginning day 29): 40 mg weekly or 80 mg every other week.
Juvenile idiopathic arthritis (JIA):
Fixed dosing:
Children ≥2 years and Adolescents:
10 kg to <15 kg: SUBQ: 10 mg every other week.
15 to <30 kg: SUBQ: 20 mg every other week.
≥30 kg: SUBQ: 40 mg every other week.
BSA-directed dosing: Note: Dosing based on trials performed with Humira product.
Children 2 to <4 years: SUBQ: 24 mg/m2/dose every other week; maximum dose: 20 mg/dose (Ref).
Children and Adolescents 4 to 17 years: SUBQ: 24 mg/m2/dose every other week; maximum dose: 40 mg/dose (Ref).
Ulcerative colitis; moderate to severe:
Fixed dosing: Children ≥5 years and Adolescents:
20 to <40 kg: SUBQ:
Initial: 80 mg on day 1, then 40 mg administered weekly for 2 weeks (a dose on day 8 and day 15).
Maintenance (beginning day 29): 40 mg every other week or 20 mg every week.
≥40 kg: SUBQ:
Initial: 160 mg on day 1 (administered as full dose on day 1 or dose split and administered over 2 consecutive days), then 80 mg administered weekly for 2 weeks (a dose on day 8 and day 15).
Maintenance (beginning day 29): 80 mg every other week or 40 mg every week.
BSA-directed dosing: Children and Adolescents: SUBQ: Initial: 92 mg/m2 (maximum dose: 160 mg/dose), then 46 mg/m2 (maximum dose: 80 mg/dose) 2 weeks later, then on day 29, begin maintenance therapy: 23 mg/m2 every other week (maximum dose: 40 mg/dose) (Ref). Note: Trials performed with Humira product.
Uveitis (noninfectious intermediate, posterior, and panuveitis):
Fixed dosing: Children ≥2 years and Adolescents:
10 kg to <15 kg: SUBQ: 10 mg every other week.
15 to <30 kg: SUBQ: 20 mg every other week.
≥30 kg: SUBQ: 40 mg every other week.
BSA-directed dosing: Children ≥4 years and Adolescents: SUBQ: 24 or 40 mg/m2/dose every 2 weeks; maximum dose 40 mg/dose (Ref). Dosing based on one prospective trial comparing 24 mg/m2/dose every 2 weeks of adalimumab (n=16, ages 6 to 12 years) to infliximab (n=17, ages 5 to 13 years) and on a retrospective trial of biologic response modifiers, including 5 patients who received adalimumab at 40 mg/m2/dose every 2 weeks. Note: Trials performed with Humira product.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Antibody development may occur with the use of tumor necrosis factor alpha inhibitors (TNFai), including adalimumab. Most frequently, autoantibodies include anti-nuclear antibody (ANA) and anti-double stranded DNA (dsDNA); less frequently, anti-ENA, anti-histone Ab, and anti-cardiolipin Ab (Ref). Frequency of autoantibody development varies depending on underlying disease, specific TNFai medication, and the duration of use; the clinical significance of asymptomatic antibody positivity is unclear (Ref). Antibody positivity may rarely result in the development of an autoimmune disorder, such as lupus-like syndrome (Ref). Symptoms may include arthralgia, myalgia, mucocutaneous symptoms (eg, skin rash), cytopenia, fatigue, fever, serositis and kidney injury (Ref). Development of an autoimmune disorder is associated with a poor treatment response of the original disease to TNFai therapy (Ref). It is unclear if the development of an autoimmune disorder is a TNFai class effect; several reports of rechallenge with the same TNFai or a different TNFai after treatment of the initial autoimmune disorder did not result in a recurrence (Ref).
Mechanism: Unknown; Postulated mechanisms include bystander activation of autoreactive lymphocytes due to drug-specific immunity, nonspecific activation of lymphocytes, direct cytotoxicity with release of autoantigens, and disruption of central T-cell tolerance (Ref).
Onset: Varied; ranged from 5 weeks to 2 years (Ref).
Risk factors:
• Longer disease duration (Ref)
• Females (Ref)
• Ulcerative colitis (Ref)
New-onset or exacerbation of central and peripheral nervous system demyelinating disease, such as multiple sclerosis, optic neuritis, acute transverse myelitis, Guillain-Barré syndrome, and chronic inflammatory demyelinating polyneuropathy may occur with tumor necrosis factor alpha inhibitors (TNFai), although causality has not been proven (Ref). Symptomatic CNS demyelination associated with TNFai may be monophasic and/or clinically isolated (Ref). Partial or complete resolution may occur after discontinuation of TNFai (Ref); however, approximately one-third of TNFai associated demyelinating episodes evolve into clinically definite multiple sclerosis (Ref).
Mechanism: Unknown; several mechanisms have been postulated, including the following: May trigger CNS demyelination directly by immune activation in genetically and/or immunologically predisposed individuals (Ref); may inhibit remyelination via TNF type-2 receptor (TNRF2) (Ref); may increase ingress of auto-reactive T cells in the CNS; may alter downstream cytokine responses; may neutralize TNF systemically but not within the CNS, creating an artificially high local concentration of brain TNF (known as sponge effect); may permit latent CNS viral infection; or may promote anti-drug antibodies and immune complexes that are contributory to demyelination events (Ref).
Onset: Varied; mean time of exposure to TNFai before onset of symptoms: 18 months (Ref).
Risk factors:
• Preexisting or recent onset central or peripheral nervous system demyelinating disease
Various cutaneous eruptions have been reported, including psoriasiform eruption (either new-onset or exacerbation), hidradenitis suppurativa, lupus-like syndrome, eczematous rash, pustular rash, lichenoid eruption, and hypersensitivity angiitis (Ref).
Mechanism: Psoriasiform eruptions, lichenoid drug eruptions: Non–dose-related; possibly related to cytokine imbalance or imbalance between tumor necrosis factor (TNF)-alpha and interferon-alpha (Ref).
Onset: Psoriasiform eruptions: Delayed: Mean 15.6 ± 10.7 months (Ref). Hidradenitis suppurativa: Delayed; median 12 months (range: 1 to 72) (Ref).
Risk factors:
• Adult females (psoriatic lesions) (Ref)
• Smoking (psoriatic lesions) (Ref)
• Males (palmoplantar pustulosis) (Ref)
• Younger patients (<40 years of age) (palmoplantar pustulosis) (Ref)
• Patients with inflammatory bowel disease compared to other inflammatory diseases (psoriasiform reactions more frequent and severe) (Ref).
• Females (hidradenitis suppurativa) (Ref)
• Cross-reactivity data among TNFai in patients who develop psoriatic lesions are conflicting (Ref)
New-onset heart failure (HF) and worsening of heart failure have been reported with tumor necrosis factor-alpha inhibitors (TNFai), including adalimumab; however, data are conflicting, and risk is unclear (Ref). Rheumatoid arthritis (RA) may be a risk factor for HF development (Ref). Some data suggest that TNFai may reduce the risk of HF in the RA population by improving inflammation, lowering disease activity, and improving surrogate markers of cardiovascular disease (Ref).
Mechanism: Not clearly established; postulated mechanisms include pro-inflammatory cytokine activation, accelerated atherosclerosis, and reduced physical activity related to the underlying rheumatologic disease (Ref). "Reverse-signaling" may occur, leading to cardiotoxic effects; TNF on cardiomyocytes of the failing heart may act as receptors, activating intracellular signaling pathways, potentiating the toxic effect of the cytokine (Ref).
Onset: Varied; median 8.5 months (range: 5 to 17 months (data with infliximab) (Ref).
Risk factors:
• Preexisting heart failure
• Higher disease activity (inflammation) (eg, disease activity score (DAS28), C-reactive protein, erythrocyte sedimentation rate) (Ref)
Reactivation of hepatitis B virus (HBV) may occur with immunosuppressive or biologic therapy, including tumor necrosis factor-alpha inhibitors (TNFai) (Ref). Reactivation of HBV may occur in both patients who are HBsAg-positive and in patients who are HBsAg-negative/HBcAb-positive with detectable HBV DNA (Ref). Criteria for HBV reactivation includes (1) a rise in HBV DNA compared to baseline (or an absolute level of HBV DNA when a baseline is unavailable) and (2) reverse seroconversion (seroreversion) from HBsAg negative to HBsAg positive for patients who are HBsAg-negative and anti-HBc–positive (Ref).
Mechanism: Inhibit stimulation of HBV specific T-lymphocytes, promoting reactivation (Ref).
Onset: Varied; 2 weeks after initiation, up to a year after discontinuation (Ref).
Risk factors:
• Males (Ref)
• Older age (Ref)
• Presence of cirrhosis (Ref)
• High baseline HBV-DNA level (Ref)
• HBeAg or HBsAg seropositivity (Ref)
• Absence of anti-HBs among patients with resolved HBV infection (Ref)
• Chronic HBV (Ref)
• Non-A HBV genotype (Ref)
• Hepatitis C, hepatitis D, or HIV co-infection (Ref)
Adalimumab has been associated with increased serum transaminases and hepatotoxicity (Ref). Cholestatic hepatitis, reactivation of hepatitis B virus, and autoimmune hepatitis have been reported (Ref). Elevated aminotransferases between 2 to 3 times the upper limit of normal may occur that are usually transient and asymptomatic (Ref). Resolution of symptoms in patients who develop an autoimmune hepatitis may require initiation of corticosteroid therapy (Ref). Immunomodulatory use, in particular methotrexate, may decrease the risk of hepatotoxicity associated with tumor necrosis factor-alpha inhibitors (TNFai) (Ref). Patients often tolerate a different TNFai (Ref); although, hepatotoxicity may recur with an alternative agent in some cases (Ref). Hepatotoxicity is more commonly associated with infliximab, as compared to adalimumab and other TNFai (Ref).
Mechanism: Unknown; idiosyncratic drug reaction (Ref), or autoimmunity due to development of autoantibodies (Ref).
Onset: Varied; ranges from 4 weeks to 52 weeks (Ref). Autoimmune hepatitis has a longer latency period than non-immune cases (16 weeks vs 10 weeks, respectively) (Ref).
Tumor necrosis factor-alpha inhibitors (TNFai) may be associated with infection (including serious infection). In clinical trials, serious infections were numerically higher among patients treated with TNFai than among patients who received placebo. Meta-analyses and observational studies have reported inconsistency in risk. One study reported an increase in serious infection in patients treated with TNFai (Ref). Another study found no increase in risk (Ref). An observational study did not demonstrate an increased infection risk among patients receiving TNFai versus comparators (Ref). Infections may present as disseminated (rather than local) disease. Active tuberculosis (including reactivation of latent tuberculosis), invasive fungal infection (including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, and pneumocystosis) and bacterial infection, viral infection, or other opportunistic infections (including legionellosis and listeriosis) have been reported.
Mechanism: Dose-related; TNFa is important in the immune response against infections, suggesting that medications that inhibit TNFa may increase the risk of infections (Ref).
Risk factors:
• Higher doses (Ref)
• Older age (Ref)
• Chronic lung or kidney disease (Ref)
• Concurrent immunosuppressants (eg, corticosteroids, methotrexate) (Ref)
• History of an opportunistic infection
• Chronic or recurrent infection
• Conditions that predispose to infections (eg, advanced or poorly controlled diabetes)
• Residence/travel in areas of endemic tuberculosis or mycoses (blastomycosis, coccidioidomycosis, histoplasmosis)
Adalimumab is associated with injection-site reactions and delayed reactions (Ref). Concurrent immunomodulators (eg, methotrexate, cyclosporine) reduce the development of anti-adalimumab antibodies and may reduce risk (Ref). Most reactions do not require discontinuation and do not recur (Ref). Cross-reactivity between tumor necrosis factor-alpha inhibitors is not well-described (Ref). Anti-infliximab antibodies do not crossreact with adalimumab; although, patients who develop anti-infliximab antibodies are more prone to develop anti-adalimumab antibodies (Ref). Adalimumab has been tolerated in patients with previous infusion reactions with infliximab (Ref). In contrast, there are reports of immediate hypersensitivity reactions with adalimumab in patients who had previous infliximab-related reactions (Ref).
Mechanism: Unknown; T-cell mediated (Ref) or IgE-mediated (Ref).
Onset: Varied; 12 to 24 hours following injection (but may occur immediately following injection). Injection-site reactions often occur within the first month of treatment and last up to 4 days (Ref).
Risk factors:
• Younger age (Ref)
Lymphoma and other malignancies (some fatal) have been reported in children and adolescents receiving tumor necrosis factor-alpha inhibitors (TNFai), including adalimumab. Half of the malignancies reported in children and adolescents were lymphomas (Hodgkin lymphoma and non-Hodgkin lymphoma), while other cases varied and included rare malignancies usually associated with immunosuppression and malignancies not typically observed in this population. Most patients were receiving concomitant immunosuppressants. Hepatosplenic T-cell lymphoma, a rare T-cell lymphoma, has been reported (some fatal), primarily in patients with Crohn disease or ulcerative colitis treated with adalimumab and who received concomitant azathioprine or mercaptopurine; reports occurred predominantly in adolescent and young adult males.
Long-term observational studies and meta-analyses indicate no association between TNFai therapy and an overall increased risk of cancer (Ref). One study reported a significant increase in lymphomas in patients with rheumatoid arthritis (RA) receiving TNFai compared to the general population. However, there was no significant increased risk of lymphomas in patients receiving TNFai compared to those receiving csDMARD or with dose, increasing time since initiation, or cumulative duration (Ref). Another study reported no difference in the risk of solid tumors in patients with RA receiving TNFai compared to those receiving csDMARDs (Ref). Other studies reported no increased risk of malignancy recurrence in patients receiving TNFai (Ref).
Mechanism: May contribute to protumor activity and suppress the anti-tumor response (Ref).
Onset: Delayed; median 30 months (range: 1 to 84 months).
Adult and pediatric patients treated with tumor necrosis factor-alpha inhibitors (TNFai) are at risk for developing active tuberculosis (TB) (including reactivated tuberculosis) (Ref). A meta-analysis of randomized controlled trials (RTC) of TNFai versus control and registry/longitudinal cohort studies of TNFai versus other DMARDs found a significant increase in TB risk in patients with rheumatoid arthritis (RA) treated with TNFai. In the non-RTC studies, incidence rates with adalimumab were higher than etanercept. Preventive treatment for latent TB infection reduced TB risk (Ref). In the RCT studies, no difference in TB rates were found; however, this failure to detect a difference in TB rates between the two groups may be due to a short observational period (Ref).
Mechanism: TNFai interfere with TNFa induction of the granuloma, which is a crucial defense mechanism in controlling TB (Ref). TNFai modulates T-cell number, function, and cytokine signaling, important for the control of TB infection (Ref).
Onset: Varied; median 3 to ~73 months (Ref).
Risk factors:
• Residence in an area with high TB prevalence (Ref)
• Known TB exposure or ongoing risk factors for TB exposure (eg, travel to areas with high TB prevalence, residence in correctional facilities, long-term care facilities, or homeless shelters, certain healthcare workers (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Skin rash (12%) (table 1)
Drug (Adalimumab) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Adalimumab) |
Number of Patients (Placebo) |
---|---|---|---|---|---|---|
12% |
6% |
Adults |
40 mg every other week |
Rheumatoid Arthritis |
705 |
690 |
Hematologic & oncologic: Positive ANA titer (12%)
Immunologic: Antibody development (3% to 26%)
Infection: Infection
Local: Injection-site reaction (5% to 20%; including bleeding at injection site, erythema at injection site, injection-site pruritus, pain at injection site, swelling at injection site) (table 2)
Drug (Adalimumab) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Adalimumab) |
Number of Patients (Placebo) |
---|---|---|---|---|---|---|
16% |
N/A |
Children and adolescents |
Either 24 mg/m2 up to maximum 40 mg every other week or 20 mg every other week (<30 kg), 40 mg every other week (≥30 kg) dependent on phase of study |
Juvenile idiopathic arthritis |
171 |
N/A |
5% |
N/A |
Children and adolescents |
High dose: 40 mg every other week (≥40 kg) or 20 mg every other week (<40 kg); low dose: 20 mg every other week (≥40 kg) or 10 mg every other week (<40 kg) |
Crohn disease |
192 |
N/A |
8% |
1% |
Adults |
40 mg every other week |
Rheumatoid Arthritis |
705 |
690 |
20% |
14% |
N/A |
N/A |
Pooled placebo-controlled clinical trials |
N/A |
N/A |
Nervous system: Headache (12%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (children and adolescents: 15%)
Respiratory: Sinusitis (11%), upper respiratory tract infection (17%)
1% to 10%:
Cardiovascular: Acute myocardial infarction (<5%), atrial fibrillation (<5%), cardiac arrhythmia (<5%), chest pain (<5%), coronary artery disease (<5%), deep vein thrombosis (<5%), hypertension (5%), hypertensive encephalopathy (<5%), palpitations (<5%), pericardial effusion (<5%), pericarditis (<5%), peripheral edema (<5%), syncope (<5%), tachycardia (<5%)
Endocrine & metabolic: Dehydration (<5%), hypercholesterolemia (6%), hyperlipidemia (7%), ketosis (<5%), menstrual disease (<5%), parathyroid disease (<5%)
Gastrointestinal: Abdominal pain (7%), cholecystitis (<5%), cholelithiasis (<5%), esophagitis (<5%), gastroenteritis (<5%), gastrointestinal hemorrhage (<5%), nausea (9%), vomiting (<5%)
Genitourinary: Cystitis (<5%), hematuria (5%), pelvic pain (<5%), urinary tract infection (8%)
Hematologic & oncologic: Adenoma (<5%), agranulocytosis (<5%), paraproteinemia (<5%), polycythemia (<5%)
Hepatic: Hepatic necrosis (<5%), increased serum alkaline phosphatase (5%)
Hypersensitivity: Hypersensitivity reaction (children and adolescents: 5% to 6%)
Infection: Herpes simplex infection (≤4%), herpes zoster infection (≤4%), serious infection (4% to 5%)
Nervous system: Confusion (<5%), myasthenia (<5%), paresthesia (<5%), subdural hematoma (<5%), torso pain (<5%), tremor (<5%)
Neuromuscular & skeletal: Arthralgia (3%), arthritis (<5%, including pyogenic arthritis), arthropathy (<5%), back pain (6%), bone disease (<5%), bone fracture (<5%), limb pain (<5%), muscle cramps (<5%), osteonecrosis (<5%), synovitis (<5%), tendinopathy (<5%)
Ophthalmic: Cataract (<5%)
Renal: Nephrolithiasis (<5%)
Respiratory: Asthma (<5%), bronchospasm (<5%), dyspnea (<5%), flu-like symptoms (7%), pharyngitis (≤4%), pleural effusion (<5%), pneumonia (≤4%), respiratory depression (<5%)
Miscellaneous: Abnormal healing (<5%), accidental injury (10%)
<1%: Neuromuscular & skeletal: Lupus-like syndrome (Schiff 2006)
Frequency not defined:
Dermatologic: Basal cell carcinoma of skin, cellulitis, erysipelas, malignant melanoma, skin granuloma (annulare; children and adolescents)
Gastrointestinal: Appendicitis
Genitourinary: Uterine hemorrhage
Hematologic & oncologic: Carcinoma (including breast, gastrointestinal, lung, skin, urogenital), malignant lymphoma, neutropenia (children and adolescents)
Hepatic: Increased serum transaminases
Infection: Atypical mycobacterial infection, bacterial infection, fungal infection (including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, and infection due to an organism in genus Pneumocystis), influenza (H1N1), opportunistic infection (including Legionella and listeriosis), parasitic infection, postoperative infection, sepsis (including catheter related sepsis), viral infection
Neuromuscular & skeletal: Myositis (children and adolescents), septic arthritis
Renal: Pyelonephritis
Respiratory: Bronchitis, nasopharyngitis, streptococcal pharyngitis (children and adolescents), tuberculosis (including reactivated tuberculosis; disseminated, miliary, lymphatic, peritoneal, and pulmonary)
Postmarketing:
Cardiovascular: Heart failure (Mansitó López 2021), pulmonary embolism, vasculitis (systemic), worsening of heart failure
Dermatologic: Alopecia, cutaneous lupus erythematosus (Gonzalez-Cuevas 2020), eczematous rash (Moustou 2009), erythema multiforme, fixed drug eruption, lichenoid eruption (Moustou 2009), Merkel cell carcinoma, psoriasiform eruption (Bae 2018a), psoriasis (including new onset, palmoplantar, pustular, or exacerbation), pustular rash (Moustou 2009), Stevens-Johnson syndrome (Mounach 2013), urticaria (Grace 2020)
Gastrointestinal: Diverticulitis of the gastrointestinal tract, gastrointestinal perforation (appendiceal perforations), intestinal perforation, pancreatitis
Hematologic & oncologic: Aplastic anemia, hepatosplenic T-cell lymphomas (children, adolescents, and young adults), leukopenia, pancytopenia, thrombocytopenia
Hepatic: Autoimmune hepatitis (Adar 2010), cholestatic hepatitis (Latus 2013), hepatic failure, hepatitis, hepatotoxicity (idiosyncratic) (Chalasani 2021)
Hypersensitivity: Anaphylaxis (Steenholdt 2012), angioedema (Hansel 2019), hypersensitivity angiitis (Amarantee 2015), nonimmune anaphylaxis
Immunologic: Sarcoidosis
Infection: Reactivation of HBV (Loomba 2017)
Nervous system: Cerebrovascular accident, demyelinating disease (peripheral; including Guillain-Barré syndrome) (Kemanetzoglou 2017), demyelinating disease of the central nervous system (including multiple sclerosis) (Kemanetzoglou 2017)
Ophthalmic: Optic neuritis
Respiratory: Interstitial lung disease (including pulmonary fibrosis)
Miscellaneous: Fever (Choi 2021)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Known hypersensitivity to adalimumab or any component of the formulation; severe infection (eg, sepsis, tuberculosis, opportunistic infection); moderate-to-severe heart failure (NYHA class III/IV)
Concerns related to adverse effects:
• Antibody formation: Formation of neutralizing anti-drug antibodies may occur with biologic tumor necrosis factor (TNF) inhibitors and may be associated with loss of efficacy (AAD-NPF [Menter 2019]).
• Hematologic disorders: Rare cases of pancytopenia and aplastic anemia have been reported with TNF-blockers. Patients must be advised to seek medical attention if they develop signs and symptoms suggestive of blood dyscrasias; discontinue if significant hematologic abnormalities are confirmed. Use with caution in patients with a history of significant hematologic abnormalities.
Disease-related concerns:
• Active infection: Do not initiate therapy in patients with an active infection, including clinically important localized infection.
• HIV: Use with caution in HIV-positive patients; TNF-α inhibitors may be appropriate in patients receiving highly active antiretroviral therapy, provided they have normal CD4 counts, no viral load, and no recent opportunistic infections (AAD-NPF [Menter 2019]).
Special populations:
• Patients with rheumatic musculoskeletal disease undergoing hip or knee replacement surgery: Hold biologic disease-modifying antirheumatic drugs (DMARDs) prior to surgery and plan surgery after the next dose is due. Surgery can occur after holding medication for 1 full dosing cycle (eg, for medications administered every 4 weeks, schedule surgery 5 weeks from last administered dose); therapy can be restarted once surgical wound shows evidence of healing (eg, no swelling, erythema, or drainage), sutures/staples are removed, and no ongoing nonsurgical site infections (typically ~14 days to reduce infection risk). Decisions to withhold therapy should be based on shared decision making; ensure the patient and their provider weigh risks of interrupting therapy and disease control versus risks of continuing therapy and surgical complications (ACR/AAHKS [Goodman 2022]).
• Surgery patients: Limited experience with patients undergoing surgical procedures while on therapy; consider long half-life with planned procedures. Monitor closely for infection.
Dosage form specific issues:
• Latex: The packaging (needle cover of prefilled syringe and autoinjector) may contain latex.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Other warnings/precautions:
• Immunizations: Patients should be brought up to date with all immunizations before initiating therapy; live vaccines should not be given concurrently. There are no data available concerning the effects of therapy on vaccination or secondary transmission of live vaccines in patients receiving therapy.
Humira 10 mg/0.1 mL, 20 mg/0.2 mL, 40 mg/0.4 mL, and 80 mg/0.8 mL formulations are citrate free. All Humira biosimilars are citrate free except for Hadlima 40 mg/0.8 mL.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Auto-injector Kit, Subcutaneous:
Hulio: Adalimumab-fkjp 40 mg/0.8 mL (1 ea) [contains polysorbate 80]
Generic: Adalimumab-adbm 40 mg/0.8 mL (1 ea)
Auto-injector Kit, Subcutaneous [preservative free]:
Abrilada: Adalimumab-afzb 40 mg/0.8 mL (1 ea) [contains edetate (edta) disodium dihydrate, polysorbate 80]
Cyltezo: Adalimumab-adbm 40 mg/0.8 mL (1 ea) [contains polysorbate 80]
Cyltezo-CD/UC/HS Starter: Adalimumab-adbm 40 mg/0.8 mL (1 ea) [contains polysorbate 80]
Cyltezo-Psoriasis Starter: Adalimumab-adbm 40 mg/0.8 mL (1 ea) [contains polysorbate 80]
Idacio: Adalimumab-aacf 40 mg/0.8 mL (1 ea) [contains polysorbate 80]
Idacio for Crohns Disease/UC: Adalimumab-aacf 40 mg/0.8 mL (1 ea) [contains polysorbate 80]
Idacio for Plaque Psoriasis: Adalimumab-aacf 40 mg/0.8 mL (1 ea) [contains polysorbate 80]
Yuflyma: Adalimumab-aaty 80 mg/0.8 mL (1 ea) [contains polysorbate 80]
Yuflyma 1-Pen Kit: Adalimumab-aaty 40 mg/0.4 mL (1 ea) [contains polysorbate 80]
Yuflyma 2-Pen Kit: Adalimumab-aaty 40 mg/0.4 mL (1 ea) [contains polysorbate 80]
Yuflyma-CD/UC/HS Starter: Adalimumab-aaty 80 mg/0.8 mL (1 ea) [contains polysorbate 80]
Generic: Adalimumab-aacf 40 mg/0.8 mL (1 ea); Adalimumab-fkjp 40 mg/0.8 mL (1 ea)
Pen-injector Kit, Subcutaneous [preservative free]:
Humira Pen: 40 mg/0.8 mL (1 ea); 40 mg/0.4 mL (1 ea); 80 mg/0.8 mL (1 ea) [contains polysorbate 80]
Humira Pen-CD/UC/HS Starter: 40 mg/0.8 mL (1 ea); 80 mg/0.8 mL (1 ea) [contains polysorbate 80]
Humira Pen-Pediatric UC Start: 80 mg/0.8 mL (1 ea) [latex free; contains polysorbate 80]
Humira Pen-Ps/UV/Adol HS Start: 40 mg/0.8 mL (1 ea) [contains polysorbate 80]
Humira Pen-Psor/Uveit Starter: 80 MG/0.8ML & 40MG/0.4ML (1 ea) [contains polysorbate 80]
Prefilled Syringe Kit, Subcutaneous:
Hulio: Adalimumab-fkjp 40 mg/0.8 mL (1 ea) [contains polysorbate 80]
Yuflyma 2-Syringe Kit: Adalimumab-aaty 40 mg/0.4 mL (1 ea) [contains polysorbate 80]
Generic: 20 mg/0.4 mL (1 ea); 40 mg/0.8 mL (1 ea); Adalimumab-adbm 10 MG/0.2 mL (1 ea)
Prefilled Syringe Kit, Subcutaneous [preservative free]:
Abrilada: Adalimumab-afzb 20 mg/0.4 mL (1 ea); Adalimumab-afzb 40 mg/0.8 mL (1 ea) [contains edetate (edta) disodium dihydrate, polysorbate 80]
Cyltezo: 20 mg/0.4 mL (1 ea); 40 mg/0.8 mL (1 ea); Adalimumab-adbm 10 MG/0.2 mL (1 ea) [contains polysorbate 80]
Hulio: Adalimumab-fkjp 20 mg/0.4 mL (1 ea) [contains polysorbate 80]
Humira: 10 mg/0.2 mL (1 ea [DSC]); 20 mg/0.4 mL (1 ea [DSC]); 40 mg/0.8 mL (1 ea); 10 mg/0.1 mL (1 ea); 20 mg/0.2 mL (1 ea); 40 mg/0.4 mL (1 ea) [contains polysorbate 80]
Humira Pediatric Crohns Start: 80 mg/0.8 mL (1 ea); 80 MG/0.8ML & 40MG/0.4ML (1 ea) [contains polysorbate 80]
Idacio: Adalimumab-aacf 40 mg/0.8 mL (1 ea) [contains polysorbate 80]
Generic: Adalimumab-fkjp 20 mg/0.4 mL (1 ea); Adalimumab-fkjp 40 mg/0.8 mL (1 ea)
Solution, Subcutaneous:
Generic: 20,000 pn unit/mL (10 mL [DSC], 50 mL [DSC])
Solution Auto-injector, Subcutaneous [preservative free]:
Amjevita: Adalimumab-atto 40 mg/0.4 mL (0.4 mL); Adalimumab-atto 80 mg/0.8 mL (0.8 mL); Adalimumab-atto 40 mg/0.8 mL (0.8 mL) [latex free; contains polysorbate 80]
Hadlima PushTouch: Adalimumab-bwwd 40 mg/0.4 mL (0.4 mL); Adalimumab-bwwd 40 mg/0.8 mL (0.8 mL)
Hyrimoz: Adalimumab-adaz 40 mg/0.4 mL (0.4 mL); Adalimumab-adaz 40 mg/0.8 mL (0.8 mL) [latex free; contains polysorbate 80]
Hyrimoz: Adalimumab-adaz 40 mg/0.4 mL (0.4 mL); Adalimumab-adaz 80 mg/0.8 mL (0.8 mL) [contains polysorbate 80]
Hyrimoz-Crohns/UC Starter: Adalimumab-adaz 80 mg/0.8 mL (0.8 mL) [contains polysorbate 80]
Hyrimoz-Plaque Psoriasis Start: Adalimumab-adaz 80 mg/0.8 mL and 40 mg/0.4 mL (1.6 mL) [contains polysorbate 80]
Generic: Adalimumab-adaz 40 mg/0.4 mL (0.4 mL)
Solution Pen-injector, Subcutaneous [preservative free]:
Yusimry: Adalimumab-aqvh 40 mg/0.8 mL (0.8 mL) [contains polysorbate 80]
Solution Prefilled Syringe, Subcutaneous:
Amjevita: Adalimumab-atto 20 mg/0.4 mL (0.4 mL); Adalimumab-atto 40 mg/0.8 mL (0.8 mL) [latex free; contains polysorbate 80]
Solution Prefilled Syringe, Subcutaneous [preservative free]:
Amjevita: Adalimumab-atto 20 mg/0.2 mL (0.2 mL); Adalimumab-atto 40 mg/0.4 mL (0.4 mL) [latex free; contains polysorbate 80]
Amjevita: Adalimumab-atto 10 mg/0.2 mL (0.2 mL) [contains polysorbate 80]
Hadlima: Adalimumab-bwwd 40 mg/0.4 mL (0.4 mL); Adalimumab-bwwd 40 mg/0.8 mL (0.8 mL)
Hyrimoz: Adalimumab-adaz 40 mg/0.4 mL (0.4 mL); Adalimumab-adaz 40 mg/0.8 mL (0.8 mL) [latex free; contains polysorbate 80]
Hyrimoz: Adalimumab-adaz 10 mg/0.1 mL (0.1 mL); Adalimumab-adaz 20 mg/0.2 mL (0.2 mL); Adalimumab-adaz 40 mg/0.4 mL (0.4 mL) [contains polysorbate 80]
Hyrimoz-Ped>/=40kg Crohn Start: Adalimumab-adaz 80 mg/0.8 mL (0.8 mL) [contains polysorbate 80]
Hyrimoz-Ped<40kg Crohn Starter: Adalimumab-adaz 80 mg/0.8 mL (1.2 mL) [contains polysorbate 80]
Generic: Adalimumab-adaz 40 mg/0.4 mL (0.4 mL)
May be product dependent
Auto-injector Kit (Abrilada Subcutaneous)
40 mg/0.8 mL (per each): $3,945.90
Auto-injector Kit (Adalimumab-aacf Subcutaneous)
40 mg/0.8 mL (per each): $1,078.80
Auto-injector Kit (Adalimumab-adbm Subcutaneous)
40 mg/0.8 mL (per each): $789.18
Auto-injector Kit (Adalimumab-fkjp Subcutaneous)
40 mg/0.8 mL (per each): $597.00
Auto-injector Kit (Cyltezo Subcutaneous)
40 mg/0.8 mL (per each): $3,945.90
Auto-injector Kit (Cyltezo-CD/UC/HS Starter Subcutaneous)
40 mg/0.8 mL (per each): $3,945.89
Auto-injector Kit (Cyltezo-Psoriasis Starter Subcutaneous)
40 mg/0.8 mL (per each): $3,945.90
Auto-injector Kit (Hulio Subcutaneous)
40 mg/0.8 mL (per each): $3,945.90
Auto-injector Kit (Idacio for Crohns Disease/UC Subcutaneous)
40 mg/0.8 mL (per each): $7,891.79
Auto-injector Kit (Idacio for Plaque Psoriasis Subcutaneous)
40 mg/0.8 mL (per each): $7,891.79
Auto-injector Kit (Idacio Subcutaneous)
40 mg/0.8 mL (per each): $7,891.79
Auto-injector Kit (Yuflyma 1-Pen Kit Subcutaneous)
40 mg/0.4 mL (per each): $3,945.90
Auto-injector Kit (Yuflyma 2-Pen Kit Subcutaneous)
40 mg/0.4 mL (per each): $7,891.80
Auto-injector Kit (Yuflyma Subcutaneous)
80 mg/0.8 mL (per each): $3,945.90
Auto-injector Kit (Yuflyma-CD/UC/HS Starter Subcutaneous)
80 mg/0.8 mL (per each): $3,945.90
Pen-injector Kit (Humira Pen Subcutaneous)
40 mg/0.4 mL (per each): $4,153.57
40 mg/0.8 mL (per each): $4,153.57
80 mg/0.8 mL (per each): $8,307.16
Pen-injector Kit (Humira Pen-CD/UC/HS Starter Subcutaneous)
40 mg/0.8 mL (per each): $4,153.59
80 mg/0.8 mL (per each): $8,307.18
Pen-injector Kit (Humira Pen-Pediatric UC Start Subcutaneous)
80 mg/0.8 mL (per each): $8,307.16
Pen-injector Kit (Humira Pen-Ps/UV/Adol HS Start Subcutaneous)
40 mg/0.8 mL (per each): $4,153.58
Pen-injector Kit (Humira Pen-Psor/Uveit Starter Subcutaneous)
80 MG/0.8ML &40MG/0.4ML (per each): $5,538.11
Prefilled Syringe Kit (Abrilada Subcutaneous)
20 mg/0.4 mL (per each): $3,945.90
40 mg/0.8 mL (per each): $3,945.90
Prefilled Syringe Kit (Adalimumab-adbm Subcutaneous)
10 mg/0.2 mL (per each): $789.18
20 mg/0.4 mL (per each): $789.18
40 mg/0.8 mL (per each): $789.18
Prefilled Syringe Kit (Adalimumab-fkjp Subcutaneous)
20 mg/0.4 mL (per each): $597.00
40 mg/0.8 mL (per each): $597.00
Prefilled Syringe Kit (Cyltezo Subcutaneous)
10 mg/0.2 mL (per each): $3,945.90
20 mg/0.4 mL (per each): $3,945.90
40 mg/0.8 mL (per each): $3,945.90
Prefilled Syringe Kit (Hulio Subcutaneous)
20 mg/0.4 mL (per each): $3,945.90
40 mg/0.8 mL (per each): $3,945.90
Prefilled Syringe Kit (Humira Pediatric Crohns Start Subcutaneous)
80 mg/0.8 mL (per each): $8,307.18
80 MG/0.8ML &40MG/0.4ML (per each): $6,230.38
Prefilled Syringe Kit (Humira Subcutaneous)
10MG/0.1ML (per each): $4,153.57
20 mg/0.2 mL (per each): $4,153.57
40 mg/0.4 mL (per each): $4,153.57
40 mg/0.8 mL (per each): $4,153.57
Prefilled Syringe Kit (Idacio Subcutaneous)
40 mg/0.8 mL (per each): $7,891.79
Prefilled Syringe Kit (Yuflyma 2-Syringe Kit Subcutaneous)
40 mg/0.4 mL (per each): $7,891.80
Solution Auto-injector (Adalimumab-adaz Subcutaneous)
40 mg/0.4 mL (per 0.4 mL): $789.18
Solution Auto-injector (Amjevita Subcutaneous)
40 mg/0.8 mL (per 0.8 mL): $1,869.11
Solution Auto-injector (Hadlima PushTouch Subcutaneous)
40 mg/0.4 mL (per 0.4 mL): $622.80
40 mg/0.8 mL (per 0.8 mL): $622.80
Solution Auto-injector (Hyrimoz Subcutaneous)
40 mg/0.4 mL (per 0.4 mL): $780.00
40 mg/0.8 mL (per 0.8 mL): $780.00
80 mg/0.8 mL (per 0.8 mL): $7,891.81
Solution Auto-injector (Hyrimoz-Crohns/UC Starter Pack Subcutaneous)
80 mg/0.8 mL (per 0.8 mL): $7,891.82
Solution Auto-injector (Hyrimoz-Plaque Psoriasis Start Subcutaneous)
80 MG/0.8ML &40MG/0.4ML (per mL): $9,864.76
Solution Pen-injector (Yusimry Subcutaneous)
40 mg/0.8 mL (per 0.8 mL): $597.00
Solution Prefilled Syringe (Adalimumab-adaz Subcutaneous)
40 mg/0.4 mL (per 0.4 mL): $789.18
Solution Prefilled Syringe (Amjevita Subcutaneous)
10 mg/0.2 mL (per 0.2 mL): $3,945.89
20 mg/0.4 mL (per 0.4 mL): $3,945.89
40 mg/0.8 mL (per 0.8 mL): $3,945.89
Solution Prefilled Syringe (Hadlima Subcutaneous)
40 mg/0.4 mL (per 0.4 mL): $622.80
40 mg/0.8 mL (per 0.8 mL): $622.80
Solution Prefilled Syringe (Hyrimoz Subcutaneous)
10MG/0.1 ML (per 0.1 mL): $3,945.90
20 mg/0.2 mL (per 0.2 mL): $3,945.90
40 mg/0.4 mL (per 0.4 mL): $780.00
40 mg/0.8 mL (per 0.8 mL): $780.00
Solution Prefilled Syringe (Hyrimoz-Ped Crohns Starter Subcutaneous)
80 mg/0.8 mL (per 0.8 mL): $7,891.82
80 MG/0.8ML &40MG/0.4ML (per mL): $9,864.76
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Auto-injector Kit, Subcutaneous:
Simlandi: 40 mg/0.4 mL (1 ea, 2 ea) [contains polysorbate 80]
Yuflyma: Adalimumab-aaty 40 mg/0.4 mL (1 ea, 2 ea, 4 ea, 6 ea); Adalimumab-aaty 80 mg/0.8 mL (1 ea) [contains polysorbate 80]
Pen-injector Kit, Subcutaneous:
Hulio: 40 mg/0.8 mL (2 ea) [contains polysorbate 80]
Prefilled Syringe Kit, Subcutaneous:
Hulio: 20 mg/0.4 mL (2 ea); 40 mg/0.8 mL (2 ea) [contains polysorbate 80]
Simlandi: 40 mg/0.4 mL (1 ea, 2 ea); 80 mg/0.8 mL (1 ea, 2 ea) [contains polysorbate 80]
Yuflyma: Adalimumab-aaty 40 mg/0.4 mL (1 ea); Adalimumab-aaty 80 mg/0.8 mL (1 ea) [contains polysorbate 80]
Solution, Subcutaneous:
Humira: 40 mg/0.8 mL (0.8 mL) [contains polysorbate 80]
Solution Auto-injector, Subcutaneous:
Abrilada: 40 mg/0.8 mL (0.8 mL) [contains edetate (edta) disodium dihydrate, polysorbate 80]
Amgevita SureClick: 40 mg/0.8 mL (0.8 mL) [contains polysorbate 80]
Hadlima PushTouch: 40 mg/0.8 mL (0.8 mL)
Hyrimoz: 40 mg/0.8 mL (0.8 mL) [contains polysorbate 80]
Idacio: 40 mg/0.8 mL (0.8 mL) [contains polysorbate 80]
Solution Pen-injector, Subcutaneous:
Humira: 40 mg/0.4 mL ([DSC]) [contains polysorbate 80]
Solution Prefilled Syringe, Subcutaneous:
Abrilada: 20 mg/0.4 mL (0.4 mL); 40 mg/0.8 mL (0.8 mL) [contains edetate (edta) disodium dihydrate, polysorbate 80]
Amgevita: 20 mg/0.4 mL (0.4 mL); 40 mg/0.8 mL (0.8 mL) [contains polysorbate 80]
Hadlima: 40 mg/0.8 mL (0.8 mL)
Humira: 20 mg/0.2 mL (0.2 mL); 40 mg/0.4 mL ([DSC]) [contains polysorbate 80]
Hyrimoz: 20 mg/0.4 mL (0.4 mL); 40 mg/0.8 mL (0.8 mL) [contains polysorbate 80]
Idacio: 40 mg/0.8 mL (0.8 mL) [contains polysorbate 80]
SUBQ: For SUBQ injection at separate sites in the thigh or lower abdomen (avoiding areas within 2 inches of navel); rotate injection sites. May leave at room temperature for ~15 to 30 minutes prior to use; do not remove cap or cover while allowing product to reach room temperature. Do not use if solution is discolored or contains particulate matter. Do not administer to skin which is red, tender, bruised, hard, or that has scars, stretch marks, or psoriasis plaques. Needle cap of the prefilled syringe or needle cover for the adalimumab pen may contain latex. Prefilled pens and syringes are available for use by patients and the full amount of the syringe should be injected (self-administration); the vial is intended for institutional use only. Vials do not contain a preservative; discard unused portion. Citrate-free formulations may be associated with less pain on injection.
SubQ: Administer subcutaneously into thigh or lower abdomen (avoid areas within 2 inches of navel); rotate injection sites. If single dose requires multiple injections, administer each injection at a separate site at least 1 inch apart. Do not administer into skin that is red, tender, bruised, or hard. May leave at room temperature for ~15 to 30 minutes prior to use; do not remove cap or cover while allowing product to reach room temperature. Do not use if solution is discolored or contains particulate matter.
Single-use vial: Intended for institutional use only; does not contain a preservative; discard unused portion.
Prefilled pens/syringe: Citrate-free formulations are available and may be associated with less pain on injection. Needle cap of the prefilled syringe or needle cover may contain latex. Pinch area of skin prepped for injection and continue to hold until injection complete. Hold pen firmly against pinched skin and press button. A loud click is heard when injection has begun. Continue to hold pen against skin until injection complete (may take 10 seconds). When injection is complete, the yellow indicator will fully appear in the window view and stop moving. See product labeling for administration details.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Abrilada (adalimumab-afzb): https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761118s007lbl.pdf#page=47
Amjevita (adalimumab-atto): https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761024s015lbl.pdf#page=50
Cyltezo (adalimumab-adbm): https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761058s018lbl.pdf#page=38
Hadlima (adalimumab-bwwd): https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761059s008lbl.pdf#page=46
Hulio (adalimumab-fkjp): https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761154s005lbl.pdf#page=57
Humira: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125057s423lbl.pdf#page=57
Hyrimoz (adalimumab-adaz): https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761071s016lbl.pdf#page=60
Idacio (adalimumab-aacf): https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761255s003lbl.pdf#page=49
Yuflyma (adalimumab-aaty): https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761219s000lbl.pdf#page=39
Yusimry (adalimumab-aqvh): https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761216s004lbl.pdf#page=56
Crohn disease, moderate to severe, induction and maintenance of remission (Humira and adalimumab biosimilars): Treatment of moderately to severely active Crohn disease in adults and pediatric patients ≥6 years of age.
Hidradenitis suppurativa, moderate to severe, refractory: Treatment of moderate to severe hidradenitis suppurativa in adults (Humira and adalimumab biosimilars) and pediatric patients ≥12 years of age (Humira only).
Juvenile idiopathic arthritis (Humira and adalimumab biosimilars): Treatment (to reduce signs/symptoms) of active polyarticular juvenile idiopathic arthritis (moderate to severe) in pediatric patients ≥2 years of age; may be used alone or in combination with methotrexate.
Plaque psoriasis, moderate to severe (Humira and adalimumab biosimilars): Treatment of chronic plaque psoriasis (moderate to severe) in adults who are candidates for systemic therapy or phototherapy, and when other systemic therapies are less appropriate (with close monitoring and regular follow-up).
Rheumatoid arthritis (Humira and adalimumab biosimilars): Treatment (to reduce signs/symptoms, induce major clinical response, inhibit progression of structural damage, and improve physical function) of active rheumatoid arthritis (moderate to severe) in adults; may be used alone or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs).
Spondyloarthritis (Humira and adalimumab biosimilars):
Axial spondyloarthritis (eg, ankylosing spondylitis): Treatment (to reduce signs/symptoms) of active ankylosing spondylitis in adults. May also be used off label for nonradiographic axial spondyloarthritis (ACR [Ward 2019]).
Psoriatic arthritis: Treatment (to reduce signs/symptoms, inhibit progression of structural damage, and improve physical function) of psoriatic arthritis (a form of peripheral spondyloarthritis) in adults; may be used alone or in combination with nonbiologic DMARDs. May also be used off label for nonpsoriatic peripheral spondyloarthritis (eg, reactive arthritis, arthritis associated with inflammatory bowel disease) (Mease 2015; Paramarta 2013).
Ulcerative colitis, moderate to severe, induction and maintenance of remission: Treatment of moderately to severely active ulcerative colitis in adults (Humira and adalimumab biosimilars) and pediatric patients ≥5 years of age (Humira only). Note: Efficacy in patients intolerant of or no longer responsive to other tumor necrosis factor blockers has not been established.
Uveitis, noninfectious: Treatment of noninfectious intermediate, posterior, and panuveitis in adults (Humira and adalimumab biosimilars [except Yuflyma]) and children ≥2 years of age (Humira only).
Note: In the United States, Abrilada (adalimumab-afzb), Amjevita (adalimumab-atto), Cyltezo (adalimumab-adbm), Hadlima (adalimumab-bwwd), Hulio (adalimumab-fkjp), Hyrimoz (adalimumab-adaz), Idacio (adalimumab-aacf), Yuflyma (adalimumab-aaty), and Yusimry (adalimumab-aqvh) have been approved as biosimilars to Humira (adalimumab). In Canada, Abrilada, Amgevita, Hadlima, Hulio, Hyrimoz, Idacio, Simlandi, and Yuflyma are also approved as biosimilars to Humira; refer to Canadian product monograph(s) for biosimilar-specific indication details.
Sarcoidosis, refractory
Adalimumab may be confused with sarilumab.
Humira may be confused with Humulin, Humalog
Humira Pen may be confused with HumaPen Memoir (used with HumaLOG)
Yuflyma may be confused with Yusimry
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abatacept: Anti-TNF Agents may enhance the immunosuppressive effect of Abatacept. Risk X: Avoid combination
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Anakinra: Anti-TNF Agents may enhance the adverse/toxic effect of Anakinra. An increased risk of serious infection during concomitant use has been reported. Risk X: Avoid combination
Anifrolumab: Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) may enhance the immunosuppressive effect of Anifrolumab. Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Belimumab: May enhance the immunosuppressive effect of Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Management: Consider alternatives to the use of belimumab with other biologic therapies. Monitor closely for increased toxicities related to additive immunosuppression (ie, infection, malignancy) if combined. Risk D: Consider therapy modification
Biologic Disease-Modifying Antirheumatic Drugs (DMARDs): May enhance the immunosuppressive effect of other Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Canakinumab: Anti-TNF Agents may enhance the adverse/toxic effect of Canakinumab. Specifically, the risk for serious infections and/or neutropenia may be increased. Risk X: Avoid combination
Certolizumab Pegol: Anti-TNF Agents may enhance the immunosuppressive effect of Certolizumab Pegol. Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CycloSPORINE (Systemic): Adalimumab may decrease the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Adalimumab may decrease the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Rilonacept: Anti-TNF Agents may enhance the adverse/toxic effect of Rilonacept. Risk X: Avoid combination
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Theophylline Derivatives: Adalimumab may decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Thiopurine Analogs: Anti-TNF Agents may enhance the adverse/toxic effect of Thiopurine Analogs. Specifically, the risk for T-cell non-Hodgkin's lymphoma (including hepatosplenic T-cell lymphoma) may be increased. Risk C: Monitor therapy
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Vedolizumab: Anti-TNF Agents may enhance the adverse/toxic effect of Vedolizumab. Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
The American Academy of Dermatology considers tumor necrosis factor (TNF) blocking agents for the treatment of psoriasis to be compatible for use in patients planning to father a child (AAD-NPF [Menter 2019]). Patients with psoriasis planning to become pregnant may continue treatment with adalimumab. Patients with well-controlled psoriasis who wish to avoid fetal exposure can consider discontinuing adalimumab 10 weeks prior to attempting to become pregnant (Rademaker 2018).
Biologics, such as adalimumab, may be continued in patients with inflammatory bowel disease (eg, Crohn disease, ulcerative colitis) planning to become pregnant (Mahadevan 2019). Treatment algorithms are available for use of biologics in patients with Crohn disease who are planning to become pregnant (Weizman 2019).
Adalimumab crosses the placenta.
Adalimumab is a humanized monoclonal antibody (IgG1). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).
Following administration to pregnant patients with inflammatory bowel disease (eg, Crohn disease, ulcerative colitis), cord blood and newborn serum concentrations of adalimumab are greater than maternal serum at delivery (Julsgaard 2016; Mahadevan 2013). The mean time to adalimumab clearance was 4 months (range: 2.9 to 5 months) in a study in 36 infants exposed in utero. The estimated mean half-life of adalimumab in these infants was 26 days (Julsgaard 2016). One case report notes adalimumab was detectable in the infant serum for 19 months following in utero exposure (Labetoulle 2018).
Based on available data, an increased risk of adverse maternal or fetal effects has not been observed following adalimumab exposure during pregnancy (Nielsen 2020). Adalimumab information from a pregnancy registry collected between 2004 and 2016 is available. Included were pregnant women with rheumatoid arthritis (RA) or Crohn disease (CD) treated with adalimumab at least during the first trimester (n=257), pregnant women with RA or CD not treated with adalimumab (disease untreated control, n=120), and pregnant women without RA or CD (healthy unexposed control, n=225); 42 cases lost to follow-up. The incidence of major birth defects was not significantly different between the study groups and no pattern of specific defects was observed. An increased risk of growth restriction or serious opportunistic infections was not associated with maternal adalimumab therapy when compared to the disease untreated controls. An increased risk of preterm delivery was observed in pregnant patients with RA or CD, regardless of adalimumab exposure (Chambers 2019). Information related to this class of medications is emerging, but based on available data, tumor necrosis factor alpha (TNFα) blocking agents are considered to have low to moderate risk when used in pregnancy (ACOG 776 2019).
The risk of immunosuppression may be increased following third trimester maternal use of TNFα blocking agents; the fetus, neonate/infant should be considered immunosuppressed for 1 to 3 months following in utero exposure (AAD-NPF [Menter 2019]). Vaccination with live vaccines (eg, rotavirus vaccine) should be avoided for the first 6 months of life if exposure to a biologic agent occurs during the third trimester of pregnancy (eg, >27 weeks' gestation) (Mahadevan 2019).
Maternal adalimumab serum concentrations remain stable as pregnancy progresses (Flanagan 2020; Seow 2017).
Inflammatory bowel disease is associated with adverse pregnancy outcomes including an increased risk of miscarriage, premature delivery, delivery of a low birth weight infant, and poor maternal weight gain. Management of maternal disease should be optimized prior to pregnancy. Treatment decreases disease flares, disease activity, and the incidence of adverse pregnancy outcomes (Mahadevan 2019).
Use of immune modulating therapies in pregnancy should be individualized to optimize maternal disease and pregnancy outcomes (ACOG 776 2019). The American Academy of Dermatology considers TNFα blocking agents for the treatment of psoriasis to be compatible with pregnancy (AAD-NPF [Menter 2019]). When treatment for inflammatory bowel disease is needed in pregnant women, appropriate biologic therapy can be continued without interruption. Serum levels should be evaluated prior to conception and optimized to avoid subtherapeutic concentrations or high levels which may increase placental transfer. Dosing can be adjusted so delivery occurs at the lowest serum concentration. For adalimumab, the final injection can be given 2 to 3 weeks prior to the estimated date of delivery (1 to 2 weeks if weekly dosing), then continued 48 hours postpartum (Mahadevan 2019).
Data collection to monitor pregnancy and infant outcomes following exposure to adalimumab is ongoing. Women exposed to adalimumab during pregnancy for the treatment of an autoimmune disease (eg, inflammatory bowel disease) may contact the OTIS Autoimmune Diseases Study at 877-311-8972.
Adalimumab is present in breast milk
Based on information from three cases, adalimumab concentrations in breast milk are 0.1% to 1% of the maternal serum concentrations (Ben-Horin 2010; Fritzsche 2012). In one case, the highest milk concentration was observed 6 days following a maternal dose of adalimumab 40 mg SubQ when maternal treatment for Crohn disease was restarted 4 weeks' postpartum (Ben-Horin 2010). The same maternal dose was used in cases two and three. Adalimumab was not measurable (<40 ng/mL) in the serum of one breastfeeding infant (9 days after the last maternal dose, 8 weeks' postpartum); serum concentrations were not evaluated in the other infant (Fritzsche 2012). In a study of 21 women, only two had detectable adalimumab in their breast milk, with maximum concentrations occurring between 12 and 24 hours after the infusion (dose not stated) (Matro 2018). An increased risk of infection has not been observed in breastfeeding infants whose mothers were using adalimumab monotherapy (Mahadevan 2012).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. However, tumor necrosis factor alpha blocking agents are considered compatible with breastfeeding (AAD-NPF [Menter 2019]; ACOG 776 2019; Mahadevan 2019).
CBC with differential (baseline); complete metabolic panel (baseline); tuberculosis (TB) screening prior to initiating and during therapy including risk factors (chest X-ray if TB positive); Hepatitis C virus/hepatitis B virus (HBV) screening prior to initiating (all patients), HBV carriers (during and for several months following therapy); HIV screening in high risk patients (baseline) (AAD-NPF [Menter 2019]); signs/symptoms of infection, hypersensitivity reaction, new autoimmune disorder (including lupus-like syndrome), or malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss). Monitor improvement of symptoms and physical function assessments.
The American Gastroenterological Association suggests reactive therapeutic drug monitoring to guide treatment changes in adult patients treated with adalimumab for active inflammatory bowel disease (eg, Crohn disease, ulcerative colitis) (Feuerstein 2017).
Inflammatory bowel disease (IBD) (eg, Crohn disease, ulcerative colitis):
Reactive therapeutic drug monitoring has been suggested to guide treatment changes in adults with active IBD.
Timing of serum sample: Draw trough <24 hours prior to next scheduled dose
Therapeutic reference range: ≥7.5 mcg/mL (Feuerstein 2017)
Adalimumab is a recombinant monoclonal antibody that binds to human tumor necrosis factor alpha (TNF-alpha), thereby interfering with binding to TNFα receptor sites and subsequent cytokine-driven inflammatory processes. Elevated TNF levels in the synovial fluid are involved in the pathologic pain and joint destruction in immune-mediated arthritis. Adalimumab decreases signs and symptoms of psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. It inhibits progression of structural damage of rheumatoid and psoriatic arthritis. Reduces signs and symptoms and maintains clinical remission in Crohn disease and ulcerative colitis; reduces epidermal thickness and inflammatory cell infiltration in plaque psoriasis.
Onset of action: Response best determined after 3 to 4 months (AAD-NPF [Menter 2019]).
Distribution: Vd: 4.7 to 6 L; Synovial fluid concentrations: 31% to 96% of serum
Bioavailability: Absolute: 64%
Half-life elimination: Terminal: ~2 weeks (range: 10 to 20 days)
Time to peak, serum: SUBQ: 131 ± 56 hours
Older adult: In patients with rheumatoid arthritis (RA), there was a trend toward lower clearance with increasing age in patients 40 to >75 years of age.
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