Adalimumab is a subcutaneous monoclonal antibody specific for tumor necrosis factor-alpha (TNF-alpha), also known as a TNF-blocker. Like other TNF-blockers, adalimumab is useful in a variety of inflammatory disorders, including dermatologic, arthritic, gastrointestinal, and ophthalmic inflammatory diseases. In adults with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) adalimumab products improve clinical signs and symptoms, inhibit the radiographic progression of structural joint damage, and improve physical function; in adults with ankylosing spondylitis (AS), adalimumab products improve clinical signs and symptoms of active disease, which can improve quality of life. For adult RA, PsA, or AS, adalimumab may be used as monotherapy; the drug may also be used with other disease-modifying antirheumatic drugs (DMARDs). The ideal combination of therapy for individual patients with inflammatory arthritis conditions is determined by treat to target strategies and severity of disease. For PsA, TNF-blockers are considered a first-line treatment, even in treatment-naive patients. In pediatric patients, adalimumab products reduce the signs and symptoms of moderately to severely active juvenile idiopathic arthritis (JIA). Adalimumab is beneficial in adults with moderate to severe plaque psoriasis including psoriasis affecting the fingernails; TNF-blockers may be used as first-line systemic treatments alone or in combination with other therapies. Other dermatologic applications include the treatment of hidradenitis suppurativa where the drug reduces total abscess and inflammatory nodule count. In ophthalmology, adalimumab has resulted in significant reductions in the risk of treatment failure in patients with non-infectious intermediate, posterior, and panuveitis. Adalimumab, like many other TNF-blockers, has been used for inflammatory bowel disease. The drug is effective in Crohn's disease (adults, pediatric patients 6 years and older) and ulcerative colitis (UC) (adults, pediatric patients 5 years and older); improvements include a reduction in the signs and symptoms of the disease and inducing clinical remission in these patients. As with all TNF-blockers, adalimumab labeling carries a boxed warning regarding the potential risks for serious infection, including tuberculosis, and potential malignancy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Administer by subcutaneous injection only.
-Available in a prefilled syringe (Humira, Abrilada, Amjevita, Cyltezo, Hadlima, Hulio, Hyrimoz, Idacio, Yusimry, Yuflyma), a prefilled pen (Humira, Abrilada, Cyltezo, Hulio, Hyrimoz, Idacio, Yusimry), and an autoinjector (Amjevita, Hadlima, Simlandi, Yuflyma) for ease of patient administration. A single-use institutional-use vial (Abrilada, Hadlima, Idacio) is available but is ONLY for use and administration within an institutional setting such as a hospital, physician's office, or clinic.
-Only an individual trained in subcutaneous drug delivery should administer the injection.
-The initial injection should be given by a trained healthcare professional. A patient or caregiver who is properly trained in the injection technique may self-inject subsequent injections using the prefilled syringe, pen, or autoinjector if the prescriber deems the action appropriate.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The solution should be clear and colorless; Abrilada may appear very light brown, Cyltezo and Yusimry may appear clear to slightly cloudy and colorless to slightly yellow, Hadlima and Yuflyma may appear pale brown, Hulio may appear pale brownish-yellow, Hyrimoz may appear slightly yellowish, and Idacio may be pale yellow. Do not use if the solution has visible particles, flakes, color, or is cloudy or milky. Check to ensure that the expiration date has not passed.
Subcutaneous Administration
-Do not shake, since irreparable damage to adalimumab may occur.
-The product may be left at room temperature for approximately 15 to 30 minutes before injecting. Do not remove the cap or cover while allowing it to reach room temperature.
-The needle cap of the Cyltezo prefilled pen and syringes contain latex. Persons allergic to natural rubber or latex should not handle the cover.
-Proper injection sites are on the front of the thighs and the abdomen. Avoid injecting the area that is 2 inches around the navel. Do not inject tender, bruised, red, stretched, or scarred skin. Also, for patients with psoriasis, do not inject directly into any raised, thick, red, or scaly skin patches or lesions.
-Rotate sites with each injection. Each subsequent injection should be at least 1 inch away from the previous injection site.
-Prefilled syringe or for a syringe filled from the institutional-use vial: Remove the needle cap. Gently squeeze and hold firm the area of the cleaned skin, and insert the needle at a 45-degree angle and let go of the skin. Ensure that adalimumab is not injected into a blood vessel by pulling back on the syringe before delivering the drug solution. If no blood appears, slowly inject the solution. NOTE: Some prefilled syringes do not contain a needle safety guard; use care when injecting and at the end of the injection in order to prevent needlestick injury.
-Prefilled pen: Remove the needle cap right before injection. Hold the pen with the activator button upwards, and gently squeeze and hold firm the area of the cleaned skin until the injection is complete. Place the pen at a 90-degree angle against the raised skin, firmly push the pen down all the way against the site, and press the activator button. Keep pushing the pen down against the skin during the injection to prevent it from moving. After the 'click' is heard, wait up to 10 seconds (40 mg pen) to 15 seconds (80 mg pen) before removing the pen from the skin. The injection has finished when the plunger is at the bottom of the pen or the yellow indicator fully appears in the window view and stops moving.
-Autoinjector: Remove the needle cap and place the base of autoinjector onto the cleaned skin at a 90-degree angle. Push the entire device down firmly to start the injection. You may hear an audible first 'click' which means the injection has started. Keep holding the autoinjector firmly against the skin until the yellow or orange indicator fills the medicine window and the indicator stops moving. After a few seconds a second audible 'click' may be heard which means the injection is complete. If the medicine window is all yellow or orange, this means the dose is complete.
-Do not rub the site where injected. Slight bleeding may occur.
-All products are single-use only; the drug solution does not contain preservatives. Immediately throw away any unused product.
-Missed dose: Administer the missed dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.
-Storage: Keep unopened product refrigerated and protect from light; DO NOT freeze. If needed (for example, when traveling), most products may be stored at room temperature [Maximum temperature: 25 degrees C (77 degrees F)] for up to 14 days. Some exemptions include the following:
--Hyrimoz: Depending on the formulation, some Hyrimoz products may be stored at room temperature up to 25 degrees C (77 degrees F) for up to 21 days, while others may be kept under these conditions for only 14 days.
-Idacio: May be stored at room temperature up to 25 degrees C (77 degrees F) for up to 28 days.
-Yuflyma: May be stored at room temperature up to 25 degrees C (77 degrees F) for up to 31 days.
-Abrilada: May be stored at room temperature up to 30 degrees C (86 degrees F) for up to 30 days.
-Discard products kept at these room temperatures if not used within the 14-day/21-day/28-day/30-day/31-day period as specified by the manufacturer. Record the date when the product is first removed from the refrigerator using the spaces provided on the carton and dose trays. Do not store in extreme heat or cold.
The most common adverse reaction in placebo-controlled trials with adalimumab in adults was injection site reactions. Among adults with rheumatoid arthritis, 8% had an injection site reaction that did not include local erythema, itching, hemorrhage, pain, or swelling, and 20% of patients developed injection site reactions such as localized erythema, pruritus, bleeding, pain, or swelling. Most injection site reactions were described as mild and generally did not necessitate drug discontinuation. Upon initiation of adalimumab in pediatric patients, the most common adverse reactions were injection site pain (6% to 19%) and injection site reaction (5% to 16%). A less commonly reported adverse event is granuloma annulare.
Cases of worsening congestive heart failure (CHF) have been observed with adalimumab, and cases of new onset CHF have been reported with other TNF-blockers. Adalimumab has not been formally studied in patients with CHF; however, in clinical trials of another TNF-blocker, a higher rate of serious CHF-related adverse reactions was observed. Cautious use of adalimumab by patients who have heart failure is advised. Among patients who received adalimumab for rheumatoid arthritis, 5% had hypertension, 6% had hypercholesterolemia, and 7% had hyperlipidemia. Chest pain (unspecified), hypertensive encephalopathy, myocardial infarction, palpitations, sinus tachycardia, atrial fibrillation, peripheral edema, arrhythmia exacerbation, coronary artery disorder, cardiac arrest, pericardial effusion, pericarditis, and syncope occurred at an incidence of less than 5% in patients treated with adalimumab.
Anaphylaxis/anaphylactic reactions and angioneurotic edema (angioedema) have been reported with adalimumab administration. If anaphylactic shock or other serious allergic reactions occur, immediately discontinue adalimumab and institute appropriate therapy. In clinical trials with adults, allergic reactions such as allergic rash, anaphylactoid reactions, fixed drug reaction, non-specified drug reaction, and urticaria have been observed in approximately 1% of patients. Non-serious hypersensitivity reactions were seen in approximately 6% of pediatric patients and included primarily localized allergic hypersensitivity reactions, allergic rash, as well as intermittent urticaria and rash. Other dermatologic events have included rash in 12% of adult adalimumab recipients, and abnormal or impaired wound healing (less than 5%). Cutaneous vasculitis, Stevens-Johnson syndrome (SJS), new or worsening psoriasis (all subtypes including pustular and palmoplantar), erythema multiforme (EM), EM with papulopustular exanthema, lichenoid skin reaction (lichen planus-like eruption), alopecia, systemic vasculitis, and sarcoidosis have been reported postmarketing.
Asthma, bronchospasm, dyspnea, decreased lung function, and pleural effusion were noted in less than 5% of patients who received adalimumab for rheumatoid arthritis. Interstitial lung disease including pulmonary fibrosis have been reported postmarketing; the relationship of these events to adalimumab has not been determined.
Rare reports of pancytopenia including aplastic anemia have occurred with TNF-blockers such as adalimumab. Reports of medically significant thrombocytopenia and leukopenia have also been infrequently received, but the causal relationship of adalimumab to hematologic adverse events is unclear. Tell patients who develop possible signs and symptoms of blood dyscrasias or infection such as persistent fever, bruising, bleeding, or pallor to seek immediate medical attention. Consider adalimumab discontinuation in patients with confirmed significant hematologic abnormalities. During placebo-controlled trials, less than 5% of 705 patients who received adalimumab had agranulocytosis, GI bleeding, subdural hematoma, leg thrombosis, or polycythemia. Metrorrhagia was noted in children, and menstrual irregularity or disorder was noted in less than 5% of adults. Pulmonary embolism and deep vein thrombosis have been reported with postmarketing use.
In 39 global clinical trails, the rate of serious infections in adult adalimumab recipients (n = 7,973) was 4.3 per 100 patient-years as compared with 2.9 per 100 patient-years among control-treated recipients (n = 4,848). Serious infections included pneumonia, septic arthritis, prosthetic and postsurgical infections, erysipelas, cellulitis, diverticulitis, and pyelonephritis. Among adalimumab recipients in 52 global controlled and uncontrolled clinical trials (n = 24,605), the rate of reported active tuberculosis (TB) was 0.2 per 100 patient-years. These trials included reports of miliary, lymphatic, peritoneal, and pulmonary TB. Most of the TB cases occurred within the first 8 months after adalimumab initiation and may reflect recrudescence of latent disease. In these global clinical trials, cases of serious opportunistic infections have been reported at an overall rate of 0.05 per 100 patient-years. Some cases of serious opportunistic infections and TB have been fatal. For adults with rheumatoid arthritis who received adalimumab (n = 705), 17% had an upper respiratory infection, 11% had sinusitis, 8% had urinary tract infection, 7% had an influenza syndrome, and less than 5% had gastroenteritis or cystitis. In clinical trials of pediatric patients receiving adalimumab for polyarticular JIA (n = 203, age 2 to 17 years) or Crohn's disease (n = 192, age 6 to 17 years), rates of infection ranged from 45% to 78%. Reported infections included upper respiratory tract infections and nasopharyngitis in patients with Crohn's disease. Reported Infections in patients with JIA were mainly mild to moderate in severity and included nasopharyngitis, bronchitis, upper respiratory tract infection, and otitis media. Serious infections were noted in 4% to 9% of pediatric patients and included cases of dental caries, varicella, herpes simplex, pneumonia, streptococcal pharyngitis, urinary tract infection, viral infection, device related sepsis, gastroenteritis (including rotavirus gastroenteritis), H1N1 influenza, disseminated histoplasmosis, and herpes zoster. Neutropenia was noted. Fever has been reported with postmarketing use. Adalimumab recipients are at increased risk for developing serious infections such as bacterial, viral, and other infections due to opportunistic pathogens; most patients who developed serious infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. The concomitant use of adalimumab and abatacept or anakinra is not recommended in the treatment of patients with rheumatoid arthritis because of a higher risk of serious infections. Closely monitor patients for the development of signs and symptoms of infection during and after adalimumab receipt. Discontinue adalimumab if a patient develops a serious infection or sepsis; infections may lead to hospitalization or death. If a patient develops a new infection during adalimumab receipt, institute a prompt and complete diagnostic workup appropriate for an immunocompromised patient and initiate appropriate antimicrobial therapy. Consider the possible development of TB in patients who tested negative for latent TB infection prior to adalimumab initiation; patients with TB have frequently presented with disseminated or extrapulmonary disease. Also, consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness. Patients with histoplasmosis or other invasive fungal infections such as coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection.
Adalimumab may cause a new primary malignancy. Malignancies, some fatal, have been reported among pediatric patients who received a TNF-blocker at 18 years of age or younger. Approximately half of the cancer cases were lymphomas including Hodgkin's and non-Hodgkin's lymphoma. Other cancers included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months of therapy (range, 1 to 84 months), and most patients were receiving concomitant immunosuppressants. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma with an aggressive and often fatal disease course, have been reported among adalimumab recipients. Most cases of HSTCL occurred in adolescent and young adult males with Crohn's disease or ulcerative colitis, and almost all had received treatment with azathioprine or 6-mercaptopurine (6MP) concomitantly with a TNF-blocker at or before 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; carefully consider the potential risk with the combination of azathioprine or 6-mercaptopurine and adalimumab. In adults, the observed rate of lymphomas was approximately 0.11 per 100 patient-years after adalimumab receipt during controlled and uncontrolled portions of clinical trials for rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and Crohn's disease. The rate is approximately 3-fold higher than expected in the general population. However, patients with rheumatoid arthritis, especially those with highly active disease, are at a higher risk for the development of lymphoma. Additionally, many patients in the clinical trials had a long duration of chronic exposure to immunosuppressant therapies, a population at greater risk for development of a secondary malignancy. In a study, after adjustment for age, gender, and rheumatoid arthritis duration, the risk of lymphoma development in patients after exposure to infliximab, etanercept, or adalimumab was no higher than the risk in patients with the disease who did not receive treatment with one of these drugs. Further, lymphomas that occurred in patients treated with a tumor necrosis factor antagonist had similar characteristics as compared with lymphomas in patients with rheumatoid arthritis who did not receive these drugs. Of note, patients in this study received a tumor necrosis factor antagonist for a maximum of 4 years. In adults, the rate of nonmelanoma skin cancer was 0.8 (95% CI, 0.52, 1.09) per 100 patient-years among adalimumab recipients as compared with 0.2 (95% CI, 0.10, 0.59) per 100 patient-years among control-treated patients. Over a median 4-month treatment period, malignancies other than non-melanoma skin cancer were observed at a rate of 0.7 (95% CI, 0.48, 1.03) per 100 patient-years among adalimumab recipients versus a rate of 0.7 (95% CI, 0.41, 1.17) per 100 patient-years among control-treated patients. The most frequently observed malignancies other than lymphoma and non-melanoma skin cancer were breast, colon, prostate, lung, and melanoma. The malignancies among adalimumab recipients were similar in type and number to what would be expected in the general US population. Postmarketing cases of adenoma, Merkel cell carcinoma, mycosis fungoides-associated follicular mucinosis without systemic involvement, and acute and chronic leukemia also exist. Before prescribing adalimumab, especially in adolescents and young adults, carefully weigh the risks and benefits of using adalimumab due to the potential increased risk for cancers including hepatosplenic T-cell lymphoma (HSTCL). Educate patients and caregivers about the signs and symptoms of malignancies such as HSTCL, so that they are aware of and can seek evaluation and treatment of any signs or symptoms such as splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss. Monitor for the emergence of malignancies when a patient has been treated with adalimumab. Examine all patients for nonmelanoma skin cancer before and during adalimumab receipt. Consider the risks and benefits of adalimumab when considering adalimumab continuation in patients who develop a malignancy.
Among adalimumab recipients, hematuria was noted in 5% of patients. Dehydration, ketosis, and kidney calculus were noted in less than 5% of adalimumab recipients. Nephrotic syndrome occurred in a patient with rheumatoid arthritis who received adalimumab 1 mg/kg up to 3 mg/kg every 2 weeks for a year. The man developed pitting edema of both legs with evidence of pleural and peritoneal fluid upon prednisone dose reduction from 10 mg daily to 2.5 mg daily. Serum albumin was 1.5 g/dL, serum creatinine was approximately 1 mg/dL, and average proteinuria was 16.7 g/24 hours. Renal biopsy results were consistent with membranous glomerulopathy. Proteinuria resolved approximately 3 months after withdrawal of adalimumab and diclofenac (dosage not provided). Diclofenac was reintroduced successfully, but adalimumab reintroduction resulted in proteinuria recurrence. Withdrawal of adalimumab and treatment with prednisone 60 mg daily and cyclophosphamide resolved the proteinuria within a week. Adalimumab was reintroduced successfully, but nephrotic syndrome developed once the patient's prednisone dose fell to 5 mg daily; a prednisone dose increase to 10 mg daily allowed for continued administration of adalimumab without proteinuria.
In clinical trial populations for adalimumab, nervous system effects such as confusion, tremor, and paresthesias each occurred at an incidence of less than 5%. Cautiously consider the use of adalimumab in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders. Rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease (e.g., multiple sclerosis) and peripheral demyelinating disease (e.g., Guillain-Barre syndrome) have been reported in patients receiving TNF-blocking agents including adalimumab. A known association exists between intermediate uveitis and central demyelinating disorders. Consider discontinuing adalimumab therapy if a nervous system demyelinating disease develops. Cerebrovascular accident (stroke) has been reported with postmarketing use.
Reactivation of hepatitis B virus (HBV) may occur in patients who are chronic HBV carriers and who take adalimumab. Viral reactivation can lead to a hepatitis B exacerbation; some cases have been fatal in some patients who took TNF-blocker therapy. Most reports of HBV reactivation have been about patients who were taking other medicines that suppress the immune system; immunosuppressant drugs may also contribute to HBV reactivation. Stop adalimumab and start effective antiviral therapy in patients who develop HBV reactivation. The safety of resuming adalimumab after control of HBV reactivation is achieved is unknown. If adalimumab is restarted, carefully monitor patients.
Severe hepatic reactions including elevated hepatic enzymes and acute hepatic failure have been reported in patients receiving TNF-blockers. Among patients who received adalimumab for rheumatoid arthritis, 9% had nausea, 7% had abdominal pain, 5% had increased alkaline phosphatase, and less than 5% had hepatic necrosis, esophagitis, cholecystitis, cholelithiasis, or vomiting. Postmarketing, diverticulitis, large bowel or GI perforation including perforations associated with diverticulitis and appendiceal perforations associated with appendicitis, pancreatitis, hepatitis, and liver failure have been reported. Elevated hepatic enzymes have been reported, although the relationship between adalimumab and the liver enzyme elevations is not clear; many patients were also taking medications that cause liver enzyme elevations such as NSAIDS and methotrexate. Among patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, alanine aminotransferase (ALT) elevations of at least 3-times the upper limit of normal (ULN) occurred in 3.5% of adalimumab recipients as compared with 1.5% of control-treated patients. In adults with ulcerative colitis, 1.5% of patients treated with adalimumab and 1% of control-treated patients had ALT elevations of at least 3-times ULN. In contrast, an identical percentage of adalimumab recipients and control-treated patients with Crohn's disease (0.9%), plaque psoriasis (1.8%), or uveitis (2.4%) had ALT elevations of at least 3-times the ULN. Further, in patients with hidradenitis suppurativa, ALT elevations of at least 3-times the ULN occurred in fewer adalimumab-treated patients (0.3%) than in control-treated patients (0.6%). In clinical trials of pediatric patients receiving adalimumab for treatment of JIA, Crohn's disease, or ulcerative colitis, ALT elevations of at least 3-times the ULN occurred in 1.1% to 4.4% of patients. In patients with JIA liver enzyme test elevations were more frequent among those treated with the combination of adalimumab and methotrexate than those treated with adalimumab alone. In general, these elevations did not lead to adalimumab discontinuation. There were no reports of ALT elevations of 3- or more times the ULN in JIA patients 2 to less than 4 years of age who received adalimumab in an open-label study. Receipt of adalimumab monotherapy or in combination with other immunosuppressive agents to patients with ankylosing spondylitis led to more patients with elevated hepatic enzymes than did receipt of placebo. At week 12, mean increases in ALT, aspartate aminotransferase (AST), and total bilirubin concentrations and a mean decrease in the alkaline phosphatase concentration were statistically significantly different between adalimumab 40 mg subcutaneously every other week and placebo recipients. Elevations in ALT were more common than elevations in AST, and most elevations were 1.5- to 3-times the ULN. However, 6 patients taking adalimumab and 1 patient taking placebo had a post-baseline ALT concentration of at least 3-times the ULN. The ALT concentration returned to normal during continued adalimumab treatment in 4 of the 6 patients. Most patients with elevated hepatic enzymes were asymptomatic, and the elevations either decreased or resolved with concomitant medication modification or adalimumab continuation or discontinuation.
Adalimumab may cause keratoderma blenorrhagicum, which is a psoriaform rash that occurs primarily on the palms and soles in some patients with reactive arthritis; keratoderma blenorrhagicum is grossly and histologically indistinguishable from pustular psoriasis. A woman developed mild erythematous, pustular skin lesions on the hypothenar eminence of her left hand and similar skin lesions on the lateral plantar surface of her left foot about 18 months after starting a TNF-blocker (etanercept) for rheumatoid arthritis. Affected skin was PCR positive for Chlamydia trachomatis chromosomal DNA. Importantly, in vitro, chlamydial replication is inversely proportional to TNF alpha concentrations. Expectantly, keratoderma blenorrhagicum has also been noted in patients who have received adalimumab and infliximab.
Myositis was noted among pediatric patients who received adalimumab. Approximately 15% of children who received adalimumab developed mild-to-moderate elevations of creatine phosphokinase (CPK). Elevations exceeding 5 times the upper limit of normal were observed in several patients. CPK concentrations decreased or returned to normal in all patients, and most patients were able to continue adalimumab without interruption. In adults with plaque psoriasis, a higher incidence of arthralgia was noted (3%) in those who received adalimumab compared to the control group (1%). Among adults with rheumatoid arthritis, back pain was noted in 6% of patients, and accidental injury was noted in 10% of patients. Extremity pain, pelvic pain, surgery, parathyroid disorder, cataracts, thorax pain, arthritis, bone disorder, bone fractures (not spontaneous), osteonecrosis, joint disorder, muscle cramps, myasthenia, pyogenic arthritis, synovitis, and tendon disorder were noted in less than 5% of patients.
Among patients who received adalimumab for rheumatoid arthritis, 12% reported a headache.
Autoantibody formation and antibodies to adalimumab have occurred during treatment with adalimumab. The impact of long-term adalimumab receipt on the development of autoimmune diseases is unknown. In rheumatoid arthritis trials, 12% of adults who received adalimumab vs. 7% of patients who received placebo developed a positive ANA titer at week 24. Two of the 3,046 patients who received adalimumab developed clinical signs suggestive of new-onset lupus-like symptoms, which improved following adalimumab discontinuation. Lupus nephritis or central nervous system symptoms have not been reported. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with adalimumab, treatment should be discontinued. Antibody formation against adalimumab during 6 to 12 months of drug receipt occurred in 5% (58 of 1,062) of patients with rheumatoid arthritis; antibodies were neutralizing in vitro. Patients who received adalimumab with methotrexate had a lower rate of antibody development (1%) than patients receiving adalimumab monotherapy (12%). Although no correlation between antibody presence and adverse events was noted, patients with antibodies had a lower ACR20 response and tended to have a higher apparent clearance than patients without antibodies to adalimumab. Among pediatric patients, adalimumab antibodies were identified in 7% to 16% of patients in the juvenile idiopathic arthritis (JIA) trials and 3% of patients in the Crohn's disease and ulcerative colitis trials. Among patients in the JIA trial receiving concomitant methotrexate, the incidence was 6% compared to 26% for those receiving adalimumab monotherapy. Among adalimumab monotherapy recipients for other indications, 3% to 13% had antibodies to adalimumab. However, due to limitations of the assay conditions, antibodies could only be detected only when serum adalimumab concentrations were less than 2 mcg/mL. Among patients whose serum adalimumab concentrations were less than 2 mcg/mL, the immunogenicity rate was 8% to 28%. A new titer-based assay (ECL assay) that can detect antibodies in all patients was used in hidradenitis suppurativa, non-infectious uveitis, and pediatric ulcerative colitis patients. Among those patients, antibodies were detected in 33% to 61% of patients. In the pediatric ulcerative colitis and hidradenitis suppurativa patients, antibodies to adalimumab were associated with reduced serum adalimumab concentrations. Based on available data, antibody formation is a common effect, but the incidence (percentage) and detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, and factors influencing sample collection quality. Paraproteinemia was noted in less than 5% of adalimumab recipients. A genomewide association study found that the HLA-DQA1*05 allele increased the risk of adalimumab antibody formation by 2-fold in patients with Crohn's disease, regardless of concomitant immunomodulator use. The formation of antibodies to adalimumab can be reduced by the use of immunomodulators.
Do not administer adalimumab to patients with a history of serious hypersensitivity reactions or anaphylaxis, including a history of angioedema, to the drug. Anaphylaxis and angioneurotic edema (angioedema) have been reported following adalimumab administration. The first dose should always be administered by a healthcare professional. Immediately discontinue adalimumab and institute appropriate therapy a serious hypersensitivity reaction occurs. Patients with latex hypersensitivity should not handle the needle cap of the Cyltezo prefilled pen or syringes, as they contain natural rubber latex.
Evaluate patients at risk for hepatitis B exacerbation before initiating TNF-blocker therapy with adalimumab. The use of TNF-blockers, including adalimumab, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus. In some instances, HBV reactivation occurring in conjunction with TNF-blocker therapy has been fatal. Exercise caution in prescribing adalimumab or other TNF-blockers for patients identified as carriers of HBV. Adequate data are not available on the safety or efficacy of treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF-blocker therapy to prevent HBV reactivation. For patients who are carriers of HBV and require treatment with TNF-blockers, closely monitor such patients for clinical and laboratory signs of active hepatitis B throughout therapy and for several months following termination of therapy. The majority of HBV reactivations have occurred in patients concomitantly receiving other medications that suppress the immune system, which may also contribute to HBV reactivation. In patients who develop HBV reactivation, stop adalimumab and initiate effective antiviral therapy with appropriate supportive treatment. The safety of resuming TNF-blocker therapy after HBV reactivation is controlled is not known. Therefore, exercise caution when considering resumption of adalimumab and monitor patients closely.
Patients who receive adalimumab are at increased risk for developing serious infections that may result in hospitalization and death, and most serious infections during adalimumab treatment have occurred in patients receiving concurrent immunosuppressives such as methotrexate and corticosteroid therapy. These infections involve multiple organ systems and include bacterial infection (Legionella and Listeria), mycobacterial infection (disseminated tuberculosis or extrapulmonary tuberculosis), fungal infection (histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, listeriosis, Pneumocystis jiroveci pneumonia), parasitic infection, viral infection (hepatitis B), and other opportunistic infections. Patients with invasive fungal infections (specifically histoplasmosis) may present with disseminated rather than localized disease. Do not initiate adalimumab in patients with an active infection, including localized infections. Consider the risks and benefits of adalimumab before initiation in patients with chronic or recurrent infection; who have been exposed to tuberculosis (TB); with a history of an opportunistic infection; who have resided or traveled in areas of endemic tuberculosis or endemic mycoses such as histoplasmosis, coccidioidomycosis, or blastomycosis. Also consider infection risk vs. treatment benefit in those with underlying conditions that may predispose them to infection (e.g., elderly and patients with advanced or uncontrolled diabetes mellitus, malignancy, bone marrow suppression, or immunosuppression). Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric antifungal therapy in patients at risk for invasive fungal illness who develop a severe systemic illness. Before initiating adalimumab and periodically during therapy, evaluate patients for active TB, TB risk factors, and test patients with a tuberculin skin test for active or latent infection. The possibility of anergy needs to be considered when interpreting the test result. If tuberculin skin testing is performed for latent TB infection, an induration size of 5 mm or greater should be considered positive even if the patient was vaccinated previously with Bacille Calmette-Guerin. Initiate treatment for latent TB before adalimumab use to reduce the risk of reactivation. Consider antituberculosis therapy before adalimumab initiation in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed and in patients who have several or highly significant risk factors for TB infection (e.g., close contact with infected persons or travel to endemic zones) and have a negative test for latent TB. Educate patients about the symptoms of infection and closely monitor them during and after adalimumab treatment for signs and symptoms of infection including TB among patients who tested negative for a latent disease before adalimumab receipt. Discontinue adalimumab in patients who develop a serious infection or sepsis.
Use adalimumab with caution in patients with congestive heart failure (CHF). Cases of worsening and new onset CHF have been reported with TNF-blockers, including adalimumab. Adalimumab has not been formally studied in patients with CHF; however, in clinical trials of another TNF-blocker, a higher rate of CHF-related adverse reactions was observed. Carefully monitor patients with heart failure who receive adalimumab.
An increased risk of new primary malignancy is associated with the use of TNF-blockers such as adalimumab; lymphoma and other malignancies have been reported in pediatric patients. Postmarketing fatal cases of hepatosplenic T-cell lymphoma have been reported mostly in adolescent and young adult males with inflammatory bowel disease such as Crohn's disease or ulcerative colitis; almost all cases have occurred in patients who had received a TNF-blocker concomitantly with either azathioprine or 6-mercaptopurine (6-MP) at or before diagnosis. However, it is uncertain whether the occurrence of hepatosplenic T-cell lymphoma is related to use of a TNF-blocker or a TNF-blocker in combination with these other immunosuppressants. Consider the risks and benefits of adalimumab before treatment initiation in patients with a known malignancy other than a successfully treated nonmelanoma skin cancer or when considering continued use of adalimumab in patients who have developed a malignancy. Use of adalimumab by patients with malignancy risk factors, a malignancy history, or current malignancy may be inadvisable. Examine all patients, especially those with a medical history of prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment for the presence of nonmelanoma skin cancer before and during adalimumab receipt. Screening for dysplasia (colonoscopy and biopsies) at regular intervals before and during adalimumab receipt may be advisable for patients with inflammatory bowel disease who are at increased risk for dysplasia or colon carcinomas such as those with long-standing ulcerative colitis or primary sclerosing cholangitis and those with a history of dysplasia or colon carcinoma. In controlled trials of other TNF-blockers in adult patients at high risk for malignancy [e.g., patients with chronic obstructive pulmonary disease (COPD) with a significant smoking history and cyclophosphamide-treated patients with Wegener's granulomatosis], a higher incidence of malignancy occurred in the TNF-blocker group as compared with the control group.
Exercise caution in considering the use of adalimumab in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders. Discontinue adalimumab if such neurological disease develops. Use of TNF blocking agents, including adalimumab, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease, including multiple sclerosis and optic neuritis, and peripheral demyelinating disease, including Guillain-Barre syndrome. There is a known association between intermediate uveitis and central demyelinating disorders. Systemic administration of TNF-blockers has not provided clinical benefit for those who have multiple sclerosis; evidence suggests that these therapies exacerbate disease activity.
Treatment with adalimumab may result in the formation of autoantibodies (e.g., positive antinuclear antibodies) and, rarely, in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with adalimumab, discontinue treatment.
Patients on adalimumab may receive concurrent vaccination, except for live vaccines. No data are available on the secondary transmission of infection by live vaccines in patients receiving adalimumab. It is recommended that pediatric patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating adalimumab therapy.
There are limited data about adalimumab use during pregnancy from a prospective cohort pregnancy registry. Data from the registry report a 10% rate of major birth defects for first-trimester use of adalimumab in pregnant women compared to a rate of 7.5% in untreated controls. These data cannot definitively establish the absence of any risk with adalimumab use during pregnancy; however, the data and the data of the OTIS pregnancy registry suggest that relative risk of major birth defects and spontaneous abortions in adalimumab-exposed women are similar between that of unexposed women with underlying disease and also healthy women. Monoclonal antibodies, like adalimumab, are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. In a study of pregnant women with inflammatory bowel disease who received their last adalimumab dose 1 to 56 days prior to delivery, cord blood adalimumab concentrations on the day of birth were higher than maternal concentrations in 9 of 10 women. Adalimumab concentrations were 0.16 to 19.7 mcg/mL in cord blood, 4.28 to 17.7 mcg/mL in infant blood, and 0 to 16.1 mcg/mL in maternal blood. Some experts for inflammatory bowel disease suggest that adalimumab not be administered in the last 3 to 4 weeks of pregnancy due to the increased placental transfer, while rheumatic expert groups suggest ideally halting adalimumab therapy at 20 weeks gestation (prior to the third trimester), and continuing later in pregnancy only if necessary/indicated. In dermatologic conditions, adalimumab use during pregnancy is only advisable for severe, recalcitrant disease. Neonates and infants exposed in utero to adalimumab should be monitored carefully after birth, as data suggest adalimumab can be detected in the serum of the exposed infants for at least 3 months after birth. Immune response in the in utero exposed infant may be affected. Consider risks and benefits prior to administering live or live-attenuated vaccines to neonates or infants exposed to adalimumab in utero. Infants exposed to biologics should not receive live vaccines for at least the first several months of life or until drug levels are undetectable, with consideration given to manufacturer and consensus recommendations, if available. In animal studies, no fetal harm or malformations were observed in cynomolgus monkeys exposed to up to 373 times the maximum recommended human dose (MRHD) of adalimumab during organogenesis and later during gestation.
Consider the benefits of breast-feeding along with the mother's clinical need for adalimumab and any potential adverse effects on the breast-fed infant from adalimumab or the underlying maternal condition before use during lactation. Limited data from published case reports describe the presence of adalimumab in human breast milk at infant doses of 0.1% to 1% of the maternal serum concentration. Published data suggests systemic exposure to the infant following breast-feeding should be low because adalimumab is a large molecule, and it is degraded in the gastrointestinal tract; however, the effects of local exposure in the gastrointestinal tract are unknown. There are no reports of adverse effects of adalimumab on the breast-fed infant and no effects on milk production. In a case report, the adalimumab peak milk concentration of 31 mcg/L was obtained 6 days after injection of a single adalimumab 40 mg dose and was 1/100th of the mother's peak serum concentration (4,300 mcg/L). The low level of adalimumab found in the breast milk in this case report would be unlikely to be significant for the infant following degradation in the gastrointestinal tract before any absorption. Experts usually consider adalimumab compatible with breast-feeding based on the low levels detected in milk and the peak milk concentration that occurs 1 to 6 days following a dose. Etanercept and infliximab may be potential alternatives to consider during breast-feeding. However, indication and patient-specific factors should be assessed before considering an alternative agent.
An increased risk of lymphoma and other cancers is associated with the use of TNF-blockers in children and adolescents, and adalimumab may affect host defenses against infection. Prior to treatment initiation, pediatric patients who will receive adalimumab should be brought up to date with all immunizations in agreement with current immunization guidelines.
Use adalimumab with caution in geriatric patients. Although no overall difference in efficacy was observed in clinical trials, the frequency of serious infection and malignancy among adalimumab-treated patients was higher in patients older than 65 years compared to their younger counterparts.
Before starting adalimumab test potential drug recipients for hepatitis C (IgG) and HIV serum status (HIV-1 and HIV-2 antibodies and HIV-1 antigen). Consider ongoing screening (e.g., annually) in people who are at increased risk for HIV or hepatitis C infection. Retest for HIV infection in any person who displays symptoms or other conditions that may suggest HIV seroconversion or infection. In patients found to be infected with HIV, consider involving relevant specialists to ensure HIV viral load is suppressed on antiretroviral therapy. Similarily, retest for viral hepatitis in any person who develops unexplained elevations in hepatic enzymes. It is recommended to consult a hepatologist when using a biological therapy in patients who are infected with hepatitis C, whether newly diagnosed or chronically infected.
Patients who undergo surgery while taking a biologic therapy, such as adalimumab, may be at greater risk for postoperative infections. In patients undergoing elective surgery, balance the risk of postoperative infection against the risk of developing a severe or unstable disease by stopping the biologic therapy. When possible, it is advised to stop the biologic therapy 3- to 5-times the half-live or the length of the treatment cycle (whichever is longer) between the last dose and the planned surgery. Restart the biologic therapy postoperatively if there is no evidence of infection and wound healing is satisfactory.
For reducing the signs and symptoms of moderately to severely active rheumatoid arthritis, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function:
Subcutaneous dosage:
Adults: 40 mg subcutaneously every other week. Persons not receiving concomitant methotrexate may derive additional benefit from increasing the dose to 40 mg subcutaneously every week or 80 mg subcutaneously every other week. Guidelines recommend a TNF blocker +/- methotrexate as an option for patients with a disease duration less than 6 months and high disease activity with poor prognostic feature presence. For patients with established disease, adding or switching to an anti-TNF biologic is an option for patients with moderate or high disease activity after 3 months of methotrexate monotherapy or DMARD combination therapy. A switch to a different anti-TNF biologic is an option for patients with moderate or high disease activity after 3 months or more of a TNF blocker or with a non-serious adverse event. Also, a switch to an anti-TNF biologic is an option for patients with moderate or high disease activity after 6 months or more of a non-TNF biologic or with a serious or non-serious adverse event to the drug. The goal is low disease activity or remission.
For the treatment of moderately to severely active polyarticular juvenile idiopathic arthritis as monotherapy or with methotrexate to reduce signs and symptoms of the disease:
Subcutaneous dosage:
Children and Adolescents 2 to 17 years weighing 30 kg or more: 40 mg subcutaneously every other week.
Subcutaneous dosage (Abrilada, Amjevita, Cyltezo, Hadlima, Hulio, Humira, Hyrimoz, Idacio, and Yuflyma):
Children 2 to 12 years and weighing 15 to 29 kg: 20 mg subcutaneously every other week.
Subcutaneous dosage (Abrilada, Amjevita, Cyltezo, Hadlima, Humira, Hyrimoz, and Idacio):
Children 2 to 12 years and weighing 10 to 14 kg: 10 mg subcutaneously every other week.
For the treatment of active psoriatic arthritis to reduce the signs and symptoms, inhibit progression of structural damage, and improve physical function:
Subcutaneous dosage:
Adults: 40 mg subcutaneously every other week. Adalimumab may be used alone or in combination with a non-biologic disease-modifying anti-rheumatic drug (DMARD). Methotrexate, glucocorticoids, NSAIDs, analgesics, or other non-biologic DMARDs may be continued during treatment.
For reducing the signs and symptoms of active ankylosing spondylitis:
Subcutaneous dosage:
Adults: 40 mg subcutaneously every other week. Methotrexate, glucocorticoids, NSAIDs, analgesics, or other non-biologic disease-modifying anti-rheumatic drug (DMARD) may be continued during treatment.
For the treatment of moderate to severe chronic plaque psoriasis in persons who are candidates for systemic therapy or phototherapy and when other systemic therapies are less appropriate:
Subcutaneous dosage:
Adults: 80 mg subcutaneously as a single dose, then 40 mg subcutaneously every other week starting 1 week after the initial dose. May increase the dose to 40 mg subcutaneously once weekly if an inadequate primary response may be due to insufficient drug exposure (e.g., known subtherapeutic drug concentrations, obesity, relapse during treatment); however, consider the increased risk for infection and adverse reactions.
-for the treatment of moderate to severe pediatric plaque psoriasis*:
Subcutaneous dosage (Humira):
Children* and Adolescents* 4 to 17 years: 0.8 mg/kg/dose (Max: 40 mg/dose) subcutaneously once weekly for 2 weeks, then 0.8 mg/kg/dose (Max: 40 mg/dose) subcutaneously every other week. Guidelines recommend adalimumab as an effective therapy in children and adolescents with moderate to severe psoriasis. Approved in Europe for children 4 years of age and older. Per European labels, if weight is 15 to 29 kg: Give 20 mg dose initially, followed by 20 mg subcutaneously given every other week, starting 1 week after the initial dose. For weight 30 kg or more: 40 mg initially, followed by 40 mg subcutaneously given every other week, starting 1 week after the initial dose. If the patient does not respond within 4 months, consider discontinuation.
For the treatment of moderately to severely active Crohn's disease:
Subcutaneous dosage:
Adults: 160 mg subcutaneously as a single dose or split over 2 consecutive days, then 80 mg subcutaneously 2 weeks later, and then 40 mg subcutaneously every other week. Aminosalicylates and/or corticosteroids may be continued during treatment. Azathioprine, 6-mercaptopurine (6-MP), or methotrexate may be continued during treatment if necessary. Guidelines strongly recommend the use of adalimumab to treat Crohn's disease that is resistant to treatment with corticosteroids. During clinical trials, receipt of 160 mg subcutaneously at week 0 and 80 mg subcutaneously at week 2 led to a Crohn's disease activity index score of 150 or less at week 4 in 36% of patients, as compared to 12% of placebo recipients (p = 0.001). In a follow-up study, patients got adalimumab 40 mg subcutaneously at week 4 and 6 and patients who were in remission at week 4 and week 8 were randomized to get adalimumab 40 mg weekly (n = 18), 40 mg every other week (n = 19), or placebo (n = 18) through week 56. The percentage of patients in remission at week 56 was 83% for the weekly group, 79% for the every other week group, and 44% for the placebo group.
Children and Adolescents 6 to 17 years weighing 40 kg or more: 160 mg subcutaneously as a single dose or split over 2 consecutive days, then 80 mg subcutaneously 2 weeks later, and then 40 mg subcutaneously every other week. Guidelines strongly recommend the use of adalimumab to treat Crohn's disease that is resistant to treatment with corticosteroids.
-for Crohn's disease in pediatric patients weighing less than 40 kg:
Subcutaneous dosage (Abrilada, Amjevita, Cyltezo, Hadlima, Hulio, Humira, Hyrimoz, Idacio, and Yuflyma):
Children and Adolescents 6 to 17 years weighing 17 to 39 kg: 80 mg subcutaneously once, then 40 mg subcutaneously 2 weeks later, and then 20 mg subcutaneously every other week. Guidelines strongly recommend the use of adalimumab to treat Crohn's disease that is resistant to treatment with corticosteroids.
For the treatment of moderately to severely active ulcerative colitis:
Subcutaneous dosage:
Adults: 160 mg subcutaneously as a single dose or 80 mg subcutaneously once daily for 2 days, then 80 mg subcutaneously on Day 15, and then 40 mg subcutaneously every other week starting on Day 29. Discontinue therapy if inadequate response by 8 weeks (Day 57). The effectiveness of adalimumab has not been established in patients who have lost response to or were intolerant to tumor necrosis factor (TNF) inhibitors. Aminosalicylates, corticosteroids, azathioprine, and 6-mercaptopurine (6-MP) may be continued during treatment. Guidelines strongly recommend adalimumab for the induction and maintenance of remission in persons with moderately to severely active ulcerative colitis.
Subcutaneous dosage (Humira only):
Children and Adolescents 5 to 17 years weighing 40 kg or more: 160 mg subcutaneously as a single dose or 80 mg subcutaneously once daily for 2 days, then 80 mg subcutaneously on Days 8 and 15, and then 40 mg subcutaneously every week or 80 mg subcutaneously every other week starting on Day 29. Continue the recommended pediatric dosage in persons who turn 18 years and are well-controlled on their current dosing regimen.
Children and Adolescents 5 to 17 years weighing 20 to 39 kg: 80 mg subcutaneously on Day 1, then 40 mg subcutaneously on Days 8 and 15, and then 20 mg subcutaneously every week or 40 mg subcutaneously every other week starting on Day 29. Continue the recommended pediatric dosage in persons who turn 18 years and are well-controlled on their current dosing regimen.
For the treatment of moderate to severe hidradenitis suppurativa:
Subcutaneous dosage (Humira):
Adults: 160 mg subcutaneously (given in 1 day or split over 2 consecutive days) followed by 80 mg subcutaneously on Day 15. Begin maintenance treatment of 40 mg subcutaneously once weekly or 80 mg subcutaneously every other week on Day 29. In 2 placebo-controlled trials evaluating patients with Hurley Stage II or III disease and with at least 3 abscesses or inflammatory nodules treated with 12 weeks of adalimumab, more patients in the adalimumab group (42% to 59%) achieved Hidradenitis Suppurativa Clinical Response (HiSCR), defined as at least a 50% reduction in total abscess and inflammatory nodule count with no increase in abscess count and no increase in draining fistula relative to baseline vs. 26% to 28% with placebo.
Children and Adolescents 12 to 17 years weighing 60 kg or more: 160 mg subcutaneously (given in 1 day or split over 2 consecutive days) followed by 80 mg subcutaneously on Day 15. Begin maintenance treatment of 40 mg subcutaneously once weekly or 80 mg subcutaneously every other week on Day 29.
Children and Adolescents 12 to 17 years weighing 30 to 59 kg: 80 mg subcutaneously on Day 1. Begin maintenance treatment of 40 mg subcutaneously once every other week on Day 8.
Subcutaneous dosage (Abrilada, Amjevita, Cyltezo, Hadlima, Hulio, Hyrimoz, Idacio, Simlandi, Yuflyma, and Yusimry):
Adults: 160 mg subcutaneously (given in 1 day or split over 2 consecutive days), followed by 80 mg subcutaneously on Day 15. Begin maintenance treatment of 40 mg subcutaneously once weekly or 80 mg subcutaneously every other week on Day 29.
For the treatment of non-infectious uveitis (including intermediate, posterior, and panuveitis):
Subcutaneous dosage (Humira):
Adults: 80 mg subcutaneously, then 40 mg subcutaneously every other week starting 1 week after the initial dose.
Children and Adolescents 2 to 17 years weighing 30 kg or more: 40 mg subcutaneously every other week.
Children and Adolescents 2 to 17 years weighing 15 to 29 kg: 20 mg subcutaneously every other week.
Children 2 to 12 years weighing 10 to 14 kg: 10 mg subcutaneously every other week.
Subcutaneous dosage (Abrilada, Amjevita, Cyltezo, Hadlima, Hulio, Hyrimoz, Idacio, Simlandi, Yuflyma, and Yusimry):
Adults: 80 mg subcutaneously on Day 1, then 40 mg subcutaneously every other week starting 1 week after the initial dose.
For the treatment of sarcoidosis*:
Subcutaneous dosage:
Adults: 40 mg subcutaneously every 1 to 2 weeks. May consider 80 to 120 mg subcutaneously once weekly for 2 weeks as loading dose.
Therapeutic Drug Monitoring:
Target concentrations of adalimumab in patients with Inflammatory Bowel Disease per guidelines
-At week 4: at least 8 to 12 mcg/mL
-Maintenance therapy: at least 8 to 12 mcg/mL
-When performing reactive therapeutic drug monitoring for secondary loss of response to adalimumab, treatment discontinuation should not be considered until a drug concentration of at least 10 to 15 mcg/mL is achieved.
Maximum Dosage Limits:
-Adults
40 mg subcutaneously every week or 80 mg subcutaneously every other week for hidradenitis suppurativa and for RA if used without concurrent methotrexate; 40 mg subcutaneously every other week for maintenance dosing for uveitis, psoriatic arthritis, Crohn's disease, plaque psoriasis, ulcerative colitis, ankylosing spondylitis, or for RA if used with methotrexate.
-Geriatric
40 mg subcutaneously every week or 80 mg subcutaneously every other week for hidradenitis suppurativa and for RA if used without concurrent methotrexate; 40 mg subcutaneously every other week for maintenance dosing for uveitis, psoriatic arthritis, Crohn's disease, plaque psoriasis, ulcerative colitis, ankylosing spondylitis, or for RA if used with methotrexate.
-Adolescents
Weighing 60 kg or more: 40 mg subcutaneously every other week for JIA, uveitis, and Crohn's disease; 40 mg subcutaneously weekly or 80 mg subcutaneously every other week for hidradenitis suppurativa or ulcerative colitis.
Weighing 40 to 59 kg: 40 mg subcutaneously every other week for JIA, uveitis, Crohn's disease, and hidradenitis suppurativa; 40 mg subcutaneously weekly or 80 mg subcutaneously every other week for ulcerative colitis.
Weighing 30 to 39 kg: 40 mg subcutaneously every other week for JIA, uveitis, and hidradenitis suppurativa; 20 mg subcutaneously every other week for Crohn's disease; 20 mg subcutaneously weekly or 40 mg subcutaneously every other week for ulcerative colitis.
Weighing 20 to 29 kg: 20 mg subcutaneously every other week for JIA, uveitis, and Crohn's disease; 20 mg subcutaneously weekly or 40 mg subcutaneously every other week for ulcerative colitis.
Weighing 17 to 19 kg: 20 mg subcutaneously every other week for JIA, uveitis, and Crohn's disease.
Weighing 15 to 16 kg: 20 mg subcutaneously every other week for JIA and uveitis.
-Children
12 years weighing 60 kg or more: 40 mg subcutaneously every other week for JIA, uveitis, and Crohn's disease; 40 mg subcutaneously weekly for hidradenitis suppurativa; 40 mg subcutaneously weekly or 80 mg subcutaneously every other week for ulcerative colitis.
12 years weighing 40 to 59 kg: 40 mg subcutaneously every other week for JIA, uveitis, Crohn's disease, and hidradenitis suppurativa; 40 mg subcutaneously weekly or 80 mg subcutaneously every other week for ulcerative colitis.
12 years weighing 30 to 39 kg: 40 mg subcutaneously every other week for JIA, uveitis, and hidradenitis suppurativa; 20 mg subcutaneously every other week for Crohn's disease; 20 mg subcutaneously weekly or 40 mg subcutaneously every other week for ulcerative colitis.
12 years weighing 20 to 29 kg: 20 mg subcutaneously every other week for JIA, uveitis, and Crohn's disease; 20 mg subcutaneously weekly or 40 mg subcutaneously every other week for ulcerative colitis.
12 years weighing 17 to 19 kg: 20 mg subcutaneously every other week for JIA, uveitis, and Crohn's disease.
12 years weighing 15 to 16 kg: 20 mg subcutaneously every other week for JIA and uveitis.
6 to 11 years weighing 40 kg or more: 40 mg subcutaneously every other week for JIA, uveitis, and Crohn's disease; 40 mg subcutaneously weekly or 80 mg subcutaneously every other week for ulcerative colitis.
6 to 11 years weighing 30 to 39 kg: 40 mg subcutaneously every other week for JIA and uveitis; 20 mg subcutaneously every other week for Crohn's disease; 20 mg subcutaneously weekly or 40 mg subcutaneously every other week for ulcerative colitis.
6 to 11 years weighing 20 to 29 kg: 20 mg subcutaneously every other week for JIA, uveitis, and Crohn's disease; 20 mg subcutaneously weekly or 40 mg subcutaneously every other week for ulcerative colitis.
6 to 11 years weighing 17 to 19 kg: 20 mg subcutaneously every other week for JIA, uveitis, and Crohn's disease.
6 to 11 years weighing 15 to 16 kg: 20 mg subcutaneously every other week for JIA and uveitis.
5 years and weighing 40 kg or more: 40 mg subcutaneously every other week for JIA and uveitis; 40 mg subcutaneously weekly or 80 mg subcutaneously every other week for ulcerative colitis.
5 years and weighing 30 to 39 kg: 40 mg subcutaneously every other week for JIA and uveitis; 20 mg subcutaneously weekly or 40 mg subcutaneously every other week for ulcerative colitis.
5 years and weighing 20 to 29 kg: 20 mg subcutaneously every other week for JIA and uveitis; 20 mg subcutaneously weekly or 40 mg subcutaneously every other week for ulcerative colitis.
5 years and weighing 15 to 19 kg: 20 mg subcutaneously every other week for JIA and uveitis.
5 years and weighing 10 to 14 kg: 10 mg subcutaneously every other week for JIA and uveitis.
2 to 4 years weighing 30 kg or more: 40 mg subcutaneously every other week for JIA and uveitis.
2 to 4 years weighing 15 to 29 kg: 20 mg subcutaneously every other week for JIA and uveitis.
2 to 4 years weighing 10 to 14 kg: 10 mg subcutaneously every other week for JIA and uveitis.
1 year or weighing less than 10 kg: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Abatacept: (Major) Concomitant use of abatacept with other biologic agents, such as tumor necrosis factor (TNF) inhibitors, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. In controlled clinical trials, patients receiving concomitant abatacept and TNF inhibitor therapy experienced more infections (63%) and serious infections (4.4%) as compared with patients treated with only TNF inhibitors (43% and 0.8%, respectively). These trials failed to demonstrate an important enhancement of efficacy with concomitant administration of abatacept with a TNF inhibitor. Monitor patients for signs of infection during the transition from TNF antagonist therapy to abatacept therapy.
Anakinra: (Major) Avoid the concomitant use of anakinra with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection with no additional clinical benefit. Data suggest a higher rate of serious infections when anakinra and a TNF inhibitor is used in combination with anakinra compared with either drug given alone. Neutropenia (1,000/mcL or less) was observed in 2% of patients receiving the combination. The use of anakinra with a TNF inhibitor in combination did not yield any additional clinical benefit as compared to the use of the TNF inhibitor alone.
Anifrolumab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Antithymocyte Globulin: (Moderate) The safety and efficacy of adalimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with adalimumab may be at a greater risk of developing an infection. Many of the serious infections occurred in patients on immunosuppressive therapy that received adalimumab.
Azathioprine: (Moderate) The safety and efficacy of adalimumab in patients with immunosuppression have not been evaluated. Patients receiving azathioprine along with adalimumab may be at a greater risk of developing an infection.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Do not administer live vaccines to adalimumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving adalimumab. Before initiation of adalimumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Adalimumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Baricitinib: (Major) Concomitant use of baricitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Belimumab: (Major) Avoid use together. Belimumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Therefore, belimumab use is not recommended in combination with TNF blockers. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Canakinumab: (Major) Avoid concomitant administration of canakinumab with tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. An increased incidence of serious infections and an increased risk of neutropenia have been associated with administration of another IL-1 blocker in combination with TNF inhibitors. Based upon the potential for similar interactions, concomitant administration of canakinumab and TNF inhibitors is not recommended.
Certolizumab pegol: (Contraindicated) Do not use certolizumab in combination with other tumor necrosis factor (TNF) modifier therapy, including adalimumab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if certolizumab is used concomitantly with adalimumab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Chikungunya Vaccine, Live: (Contraindicated) Do not administer live vaccines to adalimumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving adalimumab. Before initiation of adalimumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Adalimumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cyclophosphamide: (Moderate) The safety and efficacy of adalimumab in patients taking concomitant immunosuppressants have not been evaluated. Patients receiving cyclophosphamide along with adalimumab may be at a greater risk of developing an infection.
Cyclosporine: (Moderate) The safety and efficacy of adalimumab in patients with immunosuppression have not been evaluated. Patients receiving cyclosporine along with adalimumab may be at a greater risk of developing an infection.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Etanercept: (Contraindicated) Do not use etanercept in combination with other tumor necrosis factor (TNF) modifier therapy, including adalimumab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if etanercept is used concomitantly with adalimumab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Golimumab: (Contraindicated) Do not use golimumab in combination with other tumor necrosis factor (TNF) modifier therapy, including adalimumab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if golimumab is used concomitantly with adalimumab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Infliximab: (Contraindicated) Do not use infliximab in combination with other tumor necrosis factor (TNF) modifier therapy, including adalimumab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if infliximab is used concomitantly with adalimumab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Intranasal Influenza Vaccine: (Contraindicated) Do not administer live vaccines to adalimumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving adalimumab. Before initiation of adalimumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Adalimumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Live Vaccines: (Contraindicated) Do not administer live vaccines to adalimumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving adalimumab. Before initiation of adalimumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Adalimumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Do not administer live vaccines to adalimumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving adalimumab. Before initiation of adalimumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Adalimumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Do not administer live vaccines to adalimumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving adalimumab. Before initiation of adalimumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Adalimumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Methotrexate: (Minor) Methotrexate reduced adalimumab apparent clearance after single and multiple dosing by 29% and 44% respectively; however, data do not suggest the need for dose adjustment for either drug.
Natalizumab: (Major) Natalizumab for Crohn's disease should not be used in combination with tumor necrosis factor (TNF) modifiers. Coadministration may further increase the risk of serious infections, including progressive multifocal leukoencephalopathy and other opportunistic infections. Ordinarily, patients with mulitple sclerosis who are receiving chronic TNF-modifier therapy should not be treated with natalizumab.
Rabies Vaccine: (Major) If administered concurrently, adalimumab can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of immunosuppressive mediations, such as adalimumab, should be avoided during use of the rabies vaccine for postexposure prophylaxis. When immunosuppressive therapies must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
Rilonacept: (Contraindicated) Concurrent use of rilonacept and tumor necrosis factor (TNF) modifiers is not advised, as the risk of serious infections may be increased. Although concurrent use has not been evaluated in clinical trials, an increased incidence of serious infections and neutropenia has been associated with administration of another drug that blocks IL-1 in combination with TNF inhibitors.
Rituximab: (Major) Avoid the concomitant use of rituximab with adalimumab, a tumor necrosis factor (TNF) inhibitor; coadministration may result in additive immunosuppression and an increased risk of infection. Higher rates of serious infection were observed in patients with rheumatoid arthritis treated with rituximab who received subsequent treatment with a TNF inhibitor.
Rituximab; Hyaluronidase: (Major) Avoid the concomitant use of rituximab with adalimumab, a tumor necrosis factor (TNF) inhibitor; coadministration may result in additive immunosuppression and an increased risk of infection. Higher rates of serious infection were observed in patients with rheumatoid arthritis treated with rituximab who received subsequent treatment with a TNF inhibitor.
Rotavirus Vaccine: (Contraindicated) Do not administer live vaccines to adalimumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving adalimumab. Before initiation of adalimumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Adalimumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Sarilumab: (Major) Avoid the concomitant use of sarilumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Do not administer live vaccines to adalimumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving adalimumab. Before initiation of adalimumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Adalimumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Do not administer live vaccines to adalimumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving adalimumab. Before initiation of adalimumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Adalimumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Tocilizumab: (Major) Avoid the concomitant use of tocilizumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Tofacitinib: (Major) Concomitant use of tofacitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Tofacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Adalimumab may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of adalimumab therapy.
Typhoid Vaccine: (Contraindicated) Do not administer live vaccines to adalimumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving adalimumab. Before initiation of adalimumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Adalimumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Upadacitinib: (Major) Concomitant use of upadacitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of increased immunosuppression and increased infection risk. Upadacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Do not administer live vaccines to adalimumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving adalimumab. Before initiation of adalimumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Adalimumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Vedolizumab: (Major) Vedolizumab should not be used in combination with tumor necrosis factor (TNF) modifiers because of the potential for increased risk of progressive multifocal leukoencephalopathy and other infections. Ordinarily, patients receiving chronic immunosuppressant or immunomodulatory therapy should not be treated with vedolizumab.
Yellow Fever Vaccine, Live: (Contraindicated) Do not administer live vaccines to adalimumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving adalimumab. Before initiation of adalimumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Adalimumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Adalimumab neutralizes the biological activity of tumor necrosis factor (TNF)-alpha by binding to it and blocking its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab also lyses surface TNF expressing cells in vitro in the presence of complement. Adalimumab does not bind or inactivate lymphotoxin (TNF-beta). Tumor necrosis factor-alpha (TNF-alpha) is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Biological activities attributed to TNF-alpha include induction of pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6; enhancement of leukocyte migration by increasing endothelial layer permeability; expression of adhesion molecules by endothelial cells and leukocytes; activation of neutrophil and eosinophil functional activity; fibroblast proliferation; inhibition of osteoblast differentiation; upregulation of Fas-mediated apoptosis of osteoblasts; synthesis of prostaglandins; indirect induction of osteoclast differentiation and bone resorption; and induction of acute-phase and other liver proteins. Activated macrophages release TNF-alpha, which acts on chondrocytes, fibroblasts, and osteoclasts to release metalloproteinases (MMP) and other effector molecules that induce the migration of polymorphonuclear cells.
Elevated levels of TNF are found in the synovial fluid of patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) and play an important role in both the pathologic inflammation and the joint destruction that are hallmarks of these diseases. Increased levels of TNF are also found in psoriasis plaques. In psoriasis, treatment with adalimumab may reduce the epidermal thickness and infiltration of inflammatory cells. After treatment with adalimumab, a decrease in levels of acute-phase reactants of inflammation (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and serum cytokines (IL-6) was observed compared to baseline in patients with rheumatoid arthritis. A decrease in CRP levels was also observed in patients with Crohn's disease, ulcerative colitis, and hidradenitis suppurativa. Serum levels of matrix metalloproteinases (MMP-1 and MMP-3) that produce tissue remodeling responsible for cartilage destruction were also decreased after adalimumab administration.
Adalimumab is given by subcutaneous injection. The volume of distribution (Vd) ranged from 4.7 to 6 L following intravenous dosing in pharmacokinetic studies. The systemic clearance of adalimumab is approximately 12 mL/hour. Clearance of adalimumab does not appear to change over at least 2 years of use. The mean terminal half-life was approximately 2 weeks, ranging from 10 to 20 days across studies. Adalimumab concentrations in the synovial fluid from rheumatoid arthritis patients (n = 5) ranged from 31% to 96% of those in serum.
Affected cytochrome P450 isoenzymes and drug transporters: None
-Route-Specific Pharmacokinetics
Intravenous Route
Adalimumab displays linear kinetics over the dose range of 0.5 to 10 mg/kg after a single intravenous dose to patients with rheumatoid arthritis. After a single intravenous dose of 0.25 to 10 mg/kg to patients with rheumatoid arthritis, the mean terminal half-life was approximately 2 weeks (range, 10 to 20 days).
Subcutaneous Route
After a single 40 mg subcutaneous dose to healthy adults, the maximum serum concentration (+/- SD) of 4.7 (+/- 1.6) mcg/mL is achieved within 5.5 days (131 +/- 56 hours). The average absolute subcutaneous bioavailability is 64%. Mean serum adalimumab trough concentrations at steady state increased approximately proportionally with dose after 20, 40, and 80 mg subcutaneously every other week and every week.
After 40 mg subcutaneous every other week, mean steady-state trough concentrations in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) were 5 mcg/mL with monotherapy and 8 to 9 mcg/mL with methotrexate concomitant therapy. Adalimumab exposure is estimated to be comparable in RA patients treated with 80 mg subcutaneously every other week and in those treated with 40 mg subcutaneously every week. Similar mean steady-state trough adalimumab concentrations were noted among patients with plaque psoriasis who received adalimumab 40 mg subcutaneous every other week. Among patients with plaque psoriasis, the mean adalimumab steady-state trough concentration was approximately 5 to 6 mcg/mL during monotherapy with 40 mg subcutaneously every other week. Mean adalimumab steady-state trough concentrations were slightly higher in psoriatic arthritis (PsA) patients treated with 40 mg every other week (6 to 10 mcg/mL and 8.5 to 12 mcg/mL, without and with MTX, respectively) compared to the concentrations in RA patients treated with the same dose. The pharmacokinetics of adalimumab in patients with ankylosing spondylitis (AS) were similar to those in patients with RA. Mean steady-state trough concentrations of approximately 7 mcg/mL were observed at Weeks 24 and 56 among patients with Crohn's disease who received a maintenance dose of 40 mg subcutaneously every other week; the mean trough concentration at Weeks 2 and 4 was approximately 12 mcg/mL with a loading dose of 160 mg adalimumab on Week 0 followed by 80 mg on Week 2. In patients with ulcerative colitis (UC), the loading dose of 160 mg adalimumab on Week 0 followed by 80 mg on Week 2 achieved a mean serum adalimumab trough levels of approximately 12 mcg/mL at Week 2 and Week 4. Mean steady-state trough level of approximately 8 mcg/mL was observed at Week 52 in UC patients after receiving a dose of 40 mg every other week, and approximately 15 mcg/mL at Week 52 in UC patients who increased to adalimumab 40 mg every week. Adalimumab trough concentrations were approximately 7 to 8 mcg/mL at Weeks 2 and 4, respectively, in hidradenitis suppurativa (HS) patients after receiving 160 mcg on Week 0 followed by 80 mg on Week 2. Mean steady-state trough concentrations at Week 12 through 36 in HS patients were approximately 7 to 11 mcg/mL during treatment with adalimumab 40 mg every week. In patients with uveitis receiving adalimumab 40 mg subcutaneously every other week, the mean steady-state concentration was 8 to 10 mcg/mL.
-Special Populations
Hepatic Impairment
No pharmacokinetic data are available in patients with hepatic impairment.
Renal Impairment
No pharmacokinetic data are available in patients with renal impairment.
Pediatrics
In Study JIA-I for patients with polyarticular JIA who were 4 to 17 years of age, the mean steady-state trough serum adalimumab concentrations for patients weighing less than 30 kg and receiving 20 mg adalimumab subcutaneously every other week as monotherapy or with concomitant methotrexate (MTX) were 6.8 mcg/mL and 10.9 mcg/mL, respectively. The mean steady-state trough serum adalimumab concentrations for pediatric patients weighing 30 kg or more and receiving 40 mg adalimumab subcutaneously every other week as monotherapy or with concomitant MTX were 6.6 mcg/mL and 8.1 mcg/mL, respectively. In Study JIA-II for pediatric patients with polyarticular JIA who were 2 to 3 years of age or 4 years of age and older weighing less than 15 kg, the mean steady-state trough serum adalimumab concentrations after adalimumab subcutaneously every other week as monotherapy or with concomitant MTX were 6 mcg/mL and 7.9 mcg/mL, respectively.
In pediatric subjects with Crohn's disease (CD) weighing 40 kg or more, the mean (+/-SD) serum adalimumab concentrations were 15.7 (+/-6.5) mcg/mL at Week 4 following subcutaneous doses of 160 mg at Week 0 and 80 mg at Week 2 and the mean (+/-SD) steady-state trough serum adalimumab concentrations were 10.5 (+/-6) mcg/mL at Week 52 following subcutaneous doses of 40 mg every other week. In pediatric subjects with CD weighing less than 40 kg, the mean (+/-SD) serum adalimumab concentrations were 10.6 (+/-6.1) mcg/mL at Week 4 following subcutaneous doses of 80 mg at Week 0 and 40 mg at Week 2 and the mean (+/-SD) steady-state trough serum adalimumab concentrations were 6.9 (+/-3.6) mcg/mL at Week 52 following subcutaneous doses of 20 mg every other week.
Based on population pharmacokinetic modeling and simulation, adolescent hidradenitis suppurative patients treated with the recommended dosing regimen are expected to achieve similar adalimumab concentrations as those observed in adults.
Pediatric ulcerative colitis patients (5 to 17 years of age) treated with 0.6 mg/kg (maximum of 40 mg) subcutaneously every other week achieved a mean steady-state adalimumab trough concentration of 5 +/- 3.3 mcg/mL at treatment week 52. In patients who received 0.6 mg/kg (maximum of 40 mg) subcutaneously every week, the mean steady-state trough concentration at week 52 was 15.7 +/- 5.6 mcg/mL.
Geriatric
Population pharmacokinetic analysis in patients with rheumatoid arthritis revealed a trend toward lower adalimumab clearance with increasing age in patients 40 years to older than 75 years. These increases are not likely to be clinically significant.
Gender Differences
No gender-related pharmacokinetic differences were observed for adalimumab after correction for body weight.
Other
Analysis of population pharmacokinetic parameter values for patients with rheumatoid arthritis revealed a trend toward higher apparent clearance of adalimumab in the presence of anti-adalimumab antibodies. Similarly, in the pediatric ulcerative colitis patients and patients with hidradenitis suppurativa, the presence of antibodies to adalimumab was associated with reduced serum adalimumab concentrations. In general, the extent of reduction in serum adalimumab concentrations was greater with increasing antibody titers. Minor increases in apparent clearance are also predicted in patients receiving doses lower than the recommended dose and in patients with high rheumatoid factor or CRP concentrations. These increases in clearance are not likely to be clinically significant.