Adalimumab

Adalimumab is used to reduce pain and swelling due to certain types of arthritis (such as rheumatoid, psoriatic, juvenile idiopathic, ankylosing spondylitis). Adalimumab is also used to treat certain skin disorders (such as plaque-type psoriasis, hidradenitis suppurativa). It works by blocking a protein (tumor necrosis factor or TNF) found in the body's immune system that causes joint swelling and damage in arthritis as well as red scaly patches in psoriasis. Adalimumab belongs to a class of drugs known as TNF blockers. By reducing joint swelling, this medication helps to reduce further joint damage and preserve joint function.

• Adalimumab is also used to treat certain bowel conditions (Crohn's disease, ulcerative colitis) and a certain eye disease (uveitis).
• Adalimumab is available under the following different brand names: Abrilada, Amjevita, Cyltezo, Hadlima, Hulio, Humira, Hyrimoz, Idacio, Simlandi, Yuflyma, Yusimry, and adalimumab-atto, a biosimilar.

Adult and Pediatric Dosage Forms and Strengths

Prefilled syringe/pen

• 20mg/0.4mL (Humira, Amjevita) (pediatric)
• 40mg/0.8mL (Humira, Amjevita)

Biosimilars to Humira

• Amjevita (adalimumab-atto)

Dosage Considerations – Should be Given as Follows:

Rheumatoid Arthritis

Humira, Amjevita

• Indicated for reduction of signs and symptoms, induction of major clinical response, inhibition of progression of structural damage, and improvement of physical function in adults with moderate-to-severe active rheumatoid arthritis 40 mg subcutaneously (SC) every 2 weeks
• Dosing considerations
  • May be administered as monotherapy or combined with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs)
  • If not taken with concomitant methotrexate, additional benefit may be derived from increasing adalimumab dosing frequency to once weekly

Psoriatic Arthritis

Humira, Amjevita

• Indicated for reduction of signs and symptoms, inhibition of progression of structural damage, and improvement of physical function in adults with active psoriatic arthritis
• 40 mg subcutaneously (SC) every 2 weeks
• Dosing considerations
  • It may be administered as monotherapy or combined with methotrexate or other nonbiologic DMARDs
  • If not taken with concomitant methotrexate, additional benefit may be derived from increasing adalimumab dosing frequency to once weekly

Juvenile Idiopathic Arthritis

Humira, Amjevita

• Indicated for reduction of signs and symptoms of moderately-to-severely active polyarticular juvenile idiopathic arthritis
• May be administered with methotrexate, glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), or analgesics
• Humira
  • Children under 2 years or less than 10 kg: Safety and efficacy not established
  • Children 2 years and older
    • 10 kg to less than 15 kg: 10 mg subcutaneously (SC) every 2 weeks
    • 15 kg to less than 30 kg: 20 mg SC every 2 weeks
    • 30 kg and greater: 40 mg SC every 2 weeks
• Amjevita
  • Children under 4 years: Safety and efficacy not established
  • Children 4 years and older:
    • 15 kg to less than 30 kg: 20 mg subcutaneously (SC) every 2 weeks
    • 30 kg and greater: 40 mg SC every 2 weeks

Ankylosing Spondylitis

• Humira, Amjevita
• Indicated for reduction of signs and symptoms of active ankylosing spondylitis
• 40 mg subcutaneously (SC) every 2 weeks
• Dosing considerations
  • It may be administered as monotherapy or combined with methotrexate or other nonbiologic DMARDs
  • If not taken with concomitant methotrexate, additional benefit may be derived from increasing adalimumab dosing frequency to once weekly

Plaque Psoriasis

Humira, Amjevita

• Indicated for the treatment of moderate-to-severe chronic plaque psoriasis in patients who are candidates for systemic therapy or phototherapy and for whom other systemic therapies are inappropriate
• 80 mg subcutaneously (SC) once, then, after 1 week, 40 mg SC every 2 weeks
• Humira prescribing information includes patients with moderate-to-severe fingernail psoriasis

Crohn's Disease

• Humira, Amjevita
• Indicated for reduction of signs and symptoms and induction and maintenance of clinical remission in adults with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy; may be used in patients who have lost response to or are intolerant of infliximab
• Induction: 160 mg subcutaneously (SC) either as 4 injections of 40 mg on day 1 or as 2 injections of 40 mg daily on 2 consecutive days, then 80 mg SC 2 weeks later (day 15)
• Maintenance (beginning Week 4 [Day 29]): 40 mg SC every 2 weeks
• Dosing considerations
  • Some patients may require a weekly 40-mg dose for maintenance (Inflammatory Bowel Disease 2011 Jan 17(1):141-51; American Journal of Gastroenterology 2009;104:465-83)

Pediatric Crohn's Disease

Humira

• Indicated to reduce signs and symptoms, and achieve and maintain clinical remission in pediatric patients with moderately to severely active Crohn's disease who have had an inadequate response to corticosteroids or immunomodulators (e.g., azathioprine, 6-mercaptopurine, methotrexate)
• Children under 6 years: Safety and efficacy not established
• Children 6 years and older (17 kg to less than 40 kg)
  • Induction: 80 mg subcutaneously (SC) on Day 1 (administer as two 40 mg injections in one day); THEN 2 weeks later (Day 15) give 40 mg
  • Maintenance (beginning Week 4 [Day 29]): 20 mg SC every 2 weeks

• Children 6 years and older (greater than 40 kg)
  • Induction: 160 mg SC on Day 1 (administer as four 40 mg injections in one day or as two 40 mg injections per day for two consecutive days); THEN 2 weeks later (Day 15) give 80 mg (as two 40 mg injections in one day)
  • Maintenance (beginning Week 4 [Day 29]): 40 mg SC every 2 weeks

Ulcerative Colitis

Humira, Amjevita

• Indicated for the treatment of ulcerative colitis unresponsive to immunosuppressants (e.g., corticosteroids, azathioprine, 6-mercaptopurine [6-MP])
• Induction: 160 mg subcutaneously (SC) either as 4 injections of 40 mg on day 1 or as 2 injections of 40 mg daily on 2 consecutive days, then 80 mg SC 2 weeks later (day 15)
• Maintenance (beginning Week 4 [Day 29]): 40 mg SC every 2 weeks
• Continue maintenance dose only if evidence of clinical remission is apparent by 8 weeks of therapy

Hidradenitis Suppurativa

Humira

• Indicated for the treatment of moderate-to-severe hidradenitis suppurativa (Hurley stage 2 and Hurley stage 3 disease)
• Induction: 160 mg subcutaneously (SC) either as 4 injections of 40 mg on day 1 or as 2 injections of 40 mg daily on 2 consecutive days, then 80 mg SC 2 weeks later (day 15)
• Maintenance (beginning Week 4 [Day 29]): 40 mg SC once/week

Uveitis

Humira

• Indicated for the treatment of noninfectious intermediate, posterior, and panuveitis in adults
• 80 mg subcutaneously (SC) once, then, after 1 week, 40 mg SC every 2 weeks

Common side effects of adalimumab include:

• Injection site pain
• Upper respiratory tract infection (URTI)
• Increased creatine phosphokinase
• Headache
• Rash
• Sinus infection (sinusitis)
• Nausea
• Urinary tract infection (UTI)
• Abdominal pain
• Flulike syndrome
• Hyperlipidemia
• Back pain
• High cholesterol
• Blood in the urine
• High blood pressure (hypertension)
• Increased alkaline phosphatase

Less common side effects of adalimumab include:

• Allergic reactions
• Blood disorder (leukopenia, thrombocytopenia, pancytopenia, aplastic anemia)

• General disorders and administration site conditions: Fever
• Hepato-biliary disorders: Liver failure, hepatitis
• Immune system disorders: Sarcoidosis
• Neoplasms benign, malignant, and unspecified (including cysts and polyps): Merkel Cell Carcinoma (neuroendocrine carcinoma of the skin)
• Nervous system disorders: Demyelinating disorders (e.g., optic neuritis, Guillain-Barré syndrome), cerebrovascular accident
• Respiratory disorders: Interstitial lung disease, including pulmonary fibrosis, pulmonary embolism
• Skin reactions: Stevens-Johnson Syndrome, cutaneous vasculitis, erythema multiforme, new or worsening psoriasis (all sub-types including pustular and palmoplantar), alopecia
• Vascular disorders: Systemic vasculitis, deep vein thrombosis

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

Adalimumab has no known severe interactions with other drugs.

• Adalimumab has serious interactions with at least 67 different drugs.
• Moderate interactions of adalimumab include:
  • astragalus
  • belatacept
  • denosumab
  • echinacea
  • fingolimod
  • hydroxyurea
  • influenza virus vaccine quadrivalent, recombinant
  • influenza virus vaccine trivalent, recombinant
  • maitake
  • meningococcal group B vaccine
  • mercaptopurine
  • sipuleucel-T
• Mild interactions of adalimumab include:
  • cat's claw
  • methotrexate

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns, or for more information about this medicine.

Warnings

Serious infection risk

• Increased risk for developing serious infections resulting in hospitalization or death; most patients were taking concomitant immunosuppressants (e.g., methotrexate, corticosteroids)
• Patients older than 65 years may be at greater risk
• Discontinue if a patient develops serious infection or sepsis
• Reported infections include the following:


• (1) Active tuberculosis (TB), including reactivation of latent TB (frequently present with disseminated or extrapulmonary disease); test for latent TB before use and during therapy; treat the latent infection before use
  (2) Invasive fungal infections (e.g., histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, pneumocystosis); may present with disseminated, rather than localized, disease; antigen/antibody testing for histoplasmosis may yield negative results in some patients with active infection; initiate empiric antifungal therapy if severe systemic illness develops
  (3) Other bacterial (e.g., Legionella, Listeria), mycobacterial (e.g., tuberculosis), and viral (e.g., hepatitis B) opportunistic pathogens

Malignancy

• Lymphoma and other malignancies, some fatal, have been reported in children and adolescents treated with tumor necrosis factor (TNF) blockers
• Cases of acute and chronic leukemia have been reported in association with postmarketing TNF blocker use in rheumatoid arthritis (RA) and other indications; patients with RA may be at higher risk (approximately 2-fold) for leukemia than the general population
• Manufacturers are required to report all malignancies to FDA for complete and consistent analysis

Hepatosplenic T-cell lymphoma

• HSTCL is an aggressive, rare type of T-cell lymphoma (usually fatal)
• Rare postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL) were reported primarily in adolescent and young adult patients with Crohn disease and ulcerative colitis treated with TNF blockers
• Reports have also included 1 patient being treated for psoriasis and 2 patients being treated for RA
• Most reported cases with TNF blockers have occurred with concomitant treatment with azathioprine or 6-MP, though cases have been reported with azathioprine or 6-MP alone
• In the FDA Adverse Event Reporting System (AERS) database, the literature, and the HSTCL Cancer Survivors' Network, HSTCL cases have been identified in association with the following agents: infliximab (20), etanercept (1), adalimumab (2), infliximab/adalimumab (5), certolizumab (0), golimumab (0), azathioprine (12), 6-MP (3)

This medication contains adalimumab. Do not take Humira, Amjevita, or adalimumab-atto if you are allergic to adalimumab or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• None listed on FDA-approved label

Effects of Drug Abuse

• No information available

Short-Term Effects

• See "What Are Side Effects Associated with Using Adalimumab?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Adalimumab?"

Cautions

• Consider discontinuance if hematologic disorder occurs (thrombocytopenia, pancytopenia, leukopenia)
• Coadministration with interleukin (IL)-1 blockers (e.g., anakinra, ustekinumab) may lead to serious infections and neutropenia
• Coadministration of TNF blockers with abatacept showed an increased rate of serious infections in controlled trials as compared with TNF blockers alone
• Risk of serious infection, including tuberculosis or hepatitis B virus; despite prophylactic treatment for TB, reactivation has occurred (see Warnings)
• Possible increased risk of demyelinating disorders, including multiple sclerosis, optic neuritis, and peripheral demyelinating disease (including Guillain-Barre syndrome); discontinue therapy if any of these disorders develop
• Increased risk of lymphoma and other cancers reported in children and adolescents (see Warnings)
• Occurrence of leukemia and new-onset psoriasis reported in patients treated with TNF blockers (see Warnings)
• Potential increased risk of malignancy when coadministered with azathioprine or 6-mercaptopurine
• Enhanced safety surveillance requirements to capture malignancy data: Manufacturers are required to report all malignancies to FDA for complete and consistent analysis
• Decreases immune response of live virus vaccines; also increases the risk of infection with concomitant live virus vaccines; safety of administering live or live-attenuated vaccines in infants exposed to adalimumab in utero unknown; risks and benefits should be considered prior to vaccinate (live or live-attenuated) exposed infants
• If possible, patients with juvenile idiopathic arthritis (JIA) should be current with immunization guidelines prior to initiating adalimumab; may receive concurrent vaccinations (except for living vaccines) while taking adalimumab
• Autoimmunity may result in the formation of autoantibodies and, rarely, development of lupus-like syndrome; if a patient develops symptoms suggestive of a lupus-like syndrome following treatment with adalimumab, discontinue treatment
• Hypersensitivity reactions (e.g., anaphylaxis, angioedema) are reported rarely
• Worsening or new-onset congestive heart failure reported with TNF blockers; Exercise caution when using in patients who have heart failure; TNF alpha inhibitors should only be considered in patients with heart failure if there are no other reasonable treatment options, and then consider only in patients with compensated heart failure

Pregnancy and Lactation

• Adalimumab may be acceptable for use during pregnancy
• Either animal studies show no risk but human studies are not available or animal studies showed minor risks and human studies were done and showed no risk
• A pregnancy registry has been established for adalimumab; 1-877-311-8972
• IgG1 is actively transferred across the placenta during the third trimester of pregnancy
• Limited data from published literature indicate that adalimumab is present in low levels in human milk and is not likely to be absorbed by a breastfed infant
• Consult your doctor before breastfeeding