Humira

Antipsoriatic Monoclonal Antibodies and Others
Anti-Rheumatic Monoclonal Antibodies
Tumor Necrosis Factor (TNF)-Alpha Inhibitors

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, Yuflyma) for ease of patient administration. A single-use institutional-use vial (Humira, Abrilada, Hadlima) 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.[27939] [62997] [62998] [63793]

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 cover of some prefilled syringes, prefilled pens, or autoinjector devices (i.e., Humira, Cyltezo products) 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 indicator fills the medicine window and the yellow 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, 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 30 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 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.[27939] [62997] [62998] [63793]

pericardial effusion / Delayed / 0-5.0
myocardial infarction / Delayed / 0-5.0
arrhythmia exacerbation / Early / 0-5.0
atrial fibrillation / Early / 0-5.0
cardiac arrest / Early / 0-5.0
pericarditis / Delayed / 0-5.0
bronchospasm / Rapid / 0-5.0
pleural effusion / Delayed / 0-5.0
agranulocytosis / Delayed / 0-5.0
GI bleeding / Delayed / 0-5.0
thrombosis / Delayed / 0-5.0
hepatic necrosis / Delayed / 0-5.0
cholecystitis / Delayed / 0-5.0
GI perforation / Delayed / 0-5.0
osteonecrosis / Delayed / 0-5.0
bone fractures / Delayed / 0-5.0
anaphylactoid reactions / Rapid / 0-1.0
lupus-like symptoms / Delayed / 0-0.1
heart failure / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
pulmonary fibrosis / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
pulmonary embolism / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
lymphoma / Delayed / Incidence not known
nephrotic syndrome / Delayed / Incidence not known
proteinuria / Delayed / Incidence not known
Guillain-Barre syndrome / Delayed / Incidence not known
stroke / Early / Incidence not known
hepatitis B exacerbation / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known

antibody formation / Delayed / 1.0-61.0
hyperlipidemia / Delayed / 7.0-7.0
hypercholesterolemia / Delayed / 6.0-6.0
peripheral edema / Delayed / 0-5.0
encephalopathy / Delayed / 0-5.0
chest pain (unspecified) / Early / 0-5.0
hypertension / Early / 5.0-5.0
sinus tachycardia / Rapid / 0-5.0
palpitations / Early / 0-5.0
impaired wound healing / Delayed / 0-5.0
dyspnea / Early / 0-5.0
subdural hematoma / Early / 0-5.0
polycythemia / Delayed / 0-5.0
cystitis / Delayed / 0-5.0
hematuria / Delayed / 5.0-5.0
dehydration / Delayed / 0-5.0
confusion / Early / 0-5.0
cholelithiasis / Delayed / 0-5.0
esophagitis / Delayed / 0-5.0
synovitis / Delayed / 0-5.0
cataracts / Delayed / 0-5.0
myasthenia / Delayed / 0-5.0
elevated hepatic enzymes / Delayed / 0.3-4.4
psoriasis / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
psoriaform rash / Delayed / Incidence not known

infection / Delayed / 0-78.0
rash / Early / 1.0-12.0
headache / Early / 12.0-12.0
sinusitis / Delayed / 11.0-11.0
nausea / Early / 9.0-9.0
influenza / Delayed / 7.0-7.0
abdominal pain / Early / 7.0-7.0
back pain / Delayed / 6.0-6.0
syncope / Early / 0-5.0
menstrual irregularity / Delayed / 0-5.0
paresthesias / Delayed / 0-5.0
tremor / Early / 0-5.0
vomiting / Early / 0-5.0
muscle cramps / Delayed / 0-5.0
pelvic pain / Delayed / 0-5.0
arthralgia / Delayed / 3.0-3.0
urticaria / Rapid / 1.0-1.0
alopecia / Delayed / Incidence not known
lichen planus-like eruption / Delayed / Incidence not known
fever / Early / Incidence not known
dental caries / Delayed / Incidence not known
pharyngitis / Delayed / Incidence not known

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.[27939] [45593] [62997] [62998] [63793]

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.[27939] [35501] [62997] [62998] [63793]

ABRILADA, AMJEVITA, CYLTEZO, HADLIMA, Hulio, Hulio PEN, Humira, Hyrimoz, Idacio, YUFLYMA, YUSIMRY

Rx

TNF-alpha blocker (TNF-blocker); for subcutaneous use
Used for rheumatoid arthritis, psoriatic arthritis, polyarticular juvenile idiopathic arthritis, Crohn's disease, ulcerative colitis, plaque psoriasis, ankylosing spondylitis, hidradenitis suppurativa, and uveitis
Boxed warning regarding increased risk for serious infection and malignancy

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.[27267] [27268] [27939] [31831] [62997] [62998] [63793] 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.[56233]

40 mg subcutaneously every other week.

20 mg subcutaneously every other week.

10 mg subcutaneously every other week.

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.[27939] [62997] [62998] [63793]

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.

80 mg subcutaneously as a single dose, then 40 mg subcutaneously every other week starting 1 week after the initial dose.[27939] [62997] [62998] [63793] [33702] 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.

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.

80 mg subcutaneously once, then 40 mg subcutaneously 2 weeks later (on Day 15), and then 20 mg subcutaneously every other week (starting on Day 29).      Guidelines strongly recommend the use of adalimumab to treat Crohn's disease that is resistant to treatment with corticosteroids.

160 mg subcutaneously as a single dose or split over 2 consecutive days, then 80 mg subcutaneously 2 weeks later (Day 15), and then 40 mg subcutaneously every other week (starting on Day 29). Aminosalicylates and/or corticosteroids may be continued during treatment. Azathioprine, 6-mercaptopurine (6-MP), or methotrexate may be continued during treatment if necessary.[27939] [62997] [62998] [63793] [64397]   Guidelines strongly recommend the use of adalimumab to treat Crohn's disease that is resistant to treatment with corticosteroids.[64397] 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).[33075] 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.[33076]

160 mg subcutaneously as a single dose or split over 2 consecutive days, then 80 mg subcutaneously 2 weeks later (on Day 15), and then 40 mg subcutaneously every other week (starting on Day 29).[27939] [62997] [62998] [63793]    Guidelines strongly recommend the use of adalimumab to treat Crohn's disease that is resistant to treatment with corticosteroids.[64397]

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. [62997] [62998] [63793] Guidelines strongly recommend adalimumab for the induction and maintenance of remission in persons with moderately to severely active ulcerative colitis.[64393]

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.

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.

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.[27939]

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.[27939]

80 mg subcutaneously on Day 1. Begin maintenance treatment of 40 mg subcutaneously once every other week on Day 8.

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.

80 mg subcutaneously, then 40 mg subcutaneously every other week starting 1 week after the initial dose.[27939]

40 mg subcutaneously every other week.

20 mg subcutaneously every other week.

10 mg subcutaneously every other week.

80 mg subcutaneously on Day 1, then 40 mg subcutaneously every other week starting 1 week after the initial dose.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

ABRILADA/Adalimumab/AMJEVITA/CYLTEZO/HADLIMA/Hulio/Hulio PEN/Humira/Hyrimoz/Idacio/YUFLYMA/YUSIMRY Subcutaneous Inj Sol: 0.1mL, 0.2mL, 0.4mL, 0.8mL, 10mg, 20mg, 40mg, 80mg, 40-80mg

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.

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.

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.

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.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

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.[27939]

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.[27939] [62997] [62998] [63793] [64760] [64761]
 
Affected cytochrome P450 isoenzymes and drug transporters: None

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).[27939] [63793]

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.[27939] [62997] [62998] [63793]

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.[27939] [62997] [62998] [63793] 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.[48843] 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.[61808] [48842] [62180] [62791] 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.[27939] [48842]