Adalimumab (Humira)

Today's med: Adalimumab (a da LIM yoo mab) 

(brand name: Humira)

Drug Class: Antirheumatic: Disease modifying, Gastrointestinal agent, Monoclonal antibody, Tumor Necrosis Factor blocking agent

Other Drugs in this class: Infliximab (Remicade), Etanercept (Enbrel), Certolizumab (Cimzia), Golimumab (Simponi) Link: http://www.rheumatology.org/Practice/Clinical/Patients/Medications/Anti-TNF/

Actions: Adalimumab is a recombinant monoclonal antibody that binds to human tumor necrosis factor alpha (TNF-alpha), thereby interfering with binding to TNFα receptor sites and subsequent cytokine-driven inflammatory processes. Elevated TNF levels in the synovial fluid are involved in the pathologic pain and joint destruction in immune-mediated arthritis. Adalimumab decreases signs and symptoms of psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. It inhibits progression of structural damage of rheumatoid and psoriatic arthritis. Reduces signs and symptoms and maintains clinical remission in Crohn’s disease and ulcerative colitis; reduces epidermal thickness and inflammatory cell infiltration in plaque psoriasis.

Indications: Treatment of active rheumatoid arthritis (moderate-to-severe) and active psoriatic arthritis; may be used alone or in combination with other nonbiologic disease-modifying antirheumatic drugs (DMARDs)

Treatment of ankylosing spondylitis

Treatment of moderately- to severely-active Crohn’s disease in patients with inadequate response to conventional treatment, or patients who have lost response to or are intolerant of infliximab

Treatment of moderately- to severely-active ulcerative colitis in patients unresponsive to immunosuppressants (Note:Efficacy in patients that are intolerant or no longer responsive to other TNF blockers has not been established.)

Treatment of moderate-to-severe plaque psoriasis

Treatment of moderately- to severely-active juvenile idiopathic arthritis

Contraindications: There are no contraindications listed within the FDA-approved labeling. Canadian labeling: Hypersensitivity to adalimumab or any component of the formulation; severe infection (eg, sepsis, tuberculosis, opportunistic infection); moderate-to-severe heart failure (NYHA class III/IV)

Adverse Effects: M/C reported: injection site reaction

>10%: Central nervous system: Headache (12%)

Dermatologic: Rash (6% to 12%)

Local: Injection site reaction (12% to 20%; includes erythema, itching, hemorrhage, pain, swelling)

Neuromuscular & skeletal: CPK increased (15%)

Respiratory: Upper respiratory tract infection (17%), sinusitis (11%)

Miscellaneous: Serious infection (adults 1.4-6.7 events/100 person years, children 2 events/100 person years [Burmester, 2012]), antibodies to adalimumab (3% to 26%; significance unknown), positive ANA (12%)

5% to 10%:

Cardiovascular: Hypertension (5%)

Endocrine & metabolic: Hyperlipidemia (7%), hypercholesterolemia (6%)

Gastrointestinal: Nausea (9%), abdominal pain (7%)

Genitourinary: Urinary tract infection (8%)

Hepatic: Alkaline phosphatase increased (5%)

Local: Injection site reaction (8%; other than erythema, itching, hemorrhage, pain, swelling)

Neuromuscular & skeletal: Back pain (6%)

Renal: Hematuria (5%)

Miscellaneous: Accidental injury (10%), flu-like syndrome (7%), hypersensitivity reactions (children 6%; adults <1%)

1% to 5%:

Cardiovascular: Arrhythmia, atrial fibrillation, chest pain, CHF, coronary artery disorder, deep vein thrombosis, heart arrest, MI, palpitation, pericardial effusion, pericarditis, peripheral edema, syncope, tachycardia, vascular disorder

Central nervous system: Confusion, fever, hypertensive encephalopathy, multiple sclerosis, subdural hematoma

Dermatologic: Alopecia, cellulitis, erysipelas

Endocrine & metabolic: Dehydration, menstrual disorder, parathyroid disorder

Gastrointestinal: Diverticulitis, esophagitis, gastroenteritis, gastrointestinal hemorrhage, vomiting

Genitourinary: Cystitis, pelvic pain

Hematologic: Agranulocytosis, granulocytopenia, leukopenia, pancytopenia, paraproteinemia, polycythemia

Hepatic: Cholecystitis, cholelithiasis, hepatic necrosis

Neuromuscular & skeletal: Arthralgia, arthritis, bone fracture, bone necrosis, joint disorder, muscle cramps, myasthenia, pain in extremity, paresthesia, pyogenic arthritis, synovitis, tendon disorder, tremor

Ocular: Cataract

Renal: Kidney calculus, pyelonephritis

Respiratory: Asthma, bronchospasm, dyspnea, lung function decreased, pleural effusion, pneumonia

Miscellaneous: Adenoma, allergic reactions (1%), carcinoma (including breast, gastrointestinal, skin, urogenital), healing abnormality, herpes zoster, ketosis, lupus erythematosus syndrome, lymphoma, melanoma, postsurgical infection, sepsis, tuberculosis (reactivation of latent infection; miliary, lymphatic, peritoneal and pulmonary)

<1% (Limited to important or life-threatening): Abscess (limb, perianal), anal fistula, anaphylactoid reaction, anaphylaxis, angioedema, aplastic anemia, appendicitis, basal cell carcinoma, cerebrovascular accident, cervical dysplasia, circulatory collapse, cutaneous vasculitis, cytopenia, endometrial hyperplasia, erythema multiforme, fixed drug eruption, granuloma annulare (children and adolescents), Guillain-Barré syndrome, HBV reactivation, hepatic failure, herpes virus infection, histoplasmosis, infections (bacterial, viral, fungal and protozoal), interstitial lung disease (eg, pulmonary fibrosis), intestinal obstruction, intestinal perforation, leukemias, liver metastases, lupus-like syndrome, lymphadenopathy, lymphocytosis, mycobacterium avium complex infection, myositis (children and adolescents), necrotizing fasciitis, neutropenia, optic neuritis, ovarian cancer, pancreatitis, pharyngitis (children and adolescents), psoriasis (including new onset, palmoplantar, pustular, or exacerbation), pulmonary embolism, respiratory failure, sarcoidosis, septic arthritis, septic shock, skin ulceration, Stevens-Johnson syndrome, streptococcal pharyngitis (children and adolescents), systemic vasculitis, testicular cancer, thrombocytopenia, transaminases increased, viral meningitis

Standard Dosing:  SubQ: Children ≥4 years: Juvenile idiopathic arthritis (JIA):

U.S. labeling:

15 kg to <30 kg: 20 mg every other week

≥30 kg: 40 mg every other week

Canadian labeling: 24 mg/m² (maximum dose: 40 mg) every other week

Adults:

Ankylosing spondylitis: 40 mg every other week

Crohn’s disease:

Initial: 160 mg (given as 4 injections on day 1 or as 2 injections daily over 2 consecutive days), then 80 mg 2 weeks later (day 15)

Maintenance: 40 mg every other week beginning day 29. Note: Some patients may require 40 mg every week as maintenance therapy (Lichtenstein, 2009).

Plaque psoriasis:

Initial: 80 mg as a single dose

Maintenance: 40 mg every other week beginning 1 week after initial dose

Psoriatic arthritis: 40 mg every other week

Rheumatoid arthritis: 40 mg every other week; patients not taking methotrexate may increase dose to 40 mg every week

Ulcerative colitis:

Initial: 160 mg (given as 4 injections on day 1 or as 2 injections daily over 2 consecutive days), then 80 mg 2 weeks later (day 15)

Maintenance: 40 mg every other week beginning day 29. Note: Only continue maintenance dose in patients demonstrating clinical remission by 8 weeks (day 57) of therapy.

Administration: For SubQ injection (into thigh or lower abdomen, avoiding areas within 2 inches of navel); rotate injection sites. Do not use if solution is discolored. Do not administer to skin which is red, tender, bruised, or hard. Needle cap of the prefilled syringe may contain latex.

Monitoring Parameters

Monitor improvement of symptoms and physical function assessments. Latent TB screening prior to initiating and during therapy; signs/symptoms of infection (prior to, during, and following therapy); CBC with differential; signs/symptoms/worsening of heart failure; HBV screening prior to initiating (all patients), HBV carriers (during and for several months following therapy); signs and symptoms of hypersensitivity reaction; symptoms of lupus-like syndrome; signs/symptoms of malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss)

Warnings:

• Anaphylaxis/hypersensitivity reactions: May rarely cause hypersensitivity, anaphylaxis, anaphylactoid reactions, or angioedema; medications for the treatment of hypersensitivity reactions should be available for immediate use.

• Autoimmune disorder: Positive antinuclear antibody titers have been detected in patients (with negative baselines). Rare cases of autoimmune disorder, including lupus-like syndrome, have been reported; monitor and discontinue if symptoms develop.

• Hepatitis B: Rare reactivation of hepatitis B (HBV) has occurred in chronic carriers of the virus, usually in patients receiving concomitant immunosuppressants; evaluate for HBV prior to initiation in all patients. Monitor during and for several months following discontinuation of treatment in HBV carriers; interrupt therapy if reactivation occurs and treat appropriately with antiviral therapy; if resumption of therapy is deemed necessary, exercise caution and monitor patient closely.

• Infections: [U.S. Boxed Warning]: Patients receiving adalimumab are at increased risk for serious infections which may result in hospitalization and/or fatality; infections usually developed in patients receiving concomitant immunosuppressive agents (eg, methotrexate or corticosteroids) and may present as disseminated (rather than local) disease. Active tuberculosis (or reactivation of latent tuberculosis), invasive fungal (including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, and pneumocystosis) and bacterial, viral or other opportunistic infections (including legionellosis and listeriosis) have been reported in patients receiving TNF-blocking agents, including adalimumab. Monitor closely for signs/symptoms of infection. Discontinue for serious infection or sepsis. Consider risks versus benefits prior to use in patients with a history of chronic or recurrent infection. Consider empiric antifungal therapy in patients who are at risk for invasive fungal infection and develop severe systemic illness. Caution should be exercised when considering use in the elderly or in patients with conditions that predispose them to infections (eg, diabetes) or residence/travel from areas of endemic mycoses (blastomycosis, coccidioidomycosis, histoplasmosis), or with latent or localized infections. Do not initiate adalimumab therapy with clinically important active infection. Patients who develop a new infection while undergoing treatment should be monitored closely.

• Malignancy: [U.S. Boxed Warning]: Lymphoma and other malignancies have been reported in children and adolescent patients receiving other TNF-blocking agents. Half the cases are lymphomas (Hodgkin’s and non-Hodgkin’s) and the other cases are varied, but include malignancies not typically observed in this population. Most patients were receiving concomitant immunosuppressants. [U.S. Boxed Warning]: Hepatosplenic T-cell lymphoma (HSTCL), a rare T-cell lymphoma, has also been reported primarily in patients with Crohn’s disease or ulcerative colitis treated with adalimumab and who received concomitant azathioprine or mercaptopurine; reports occurred predominantly in adolescent and young adult males. Use may affect defenses against malignancies; impact on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis has been previously associated with an increased rate of lymphoma. A higher incidence of nonmelanoma skin cancers was noted in adalimumab-treated patients (0.7/100 patient years), when compared to the control group (0.2/100 patient years). Hepatosplenic T-cell lymphoma (HSTCL), a rare T-cell lymphoma, has also been associated with TNF-blocking agents, primarily reported in adolescent and young adult males with Crohn’s disease or ulcerative colitis.

• Pancytopenia: Rare cases of pancytopenia (including aplastic anemia) have been reported with TNF-blocking agents; with significant hematologic abnormalities, consider discontinuing therapy.

• Tuberculosis: Tuberculosis (disseminated or extrapulmonary) has been reactivated while on adalimumab; most cases have been reported within the first 8 months of treatment. Doses higher than recommended are associated with an increased risk for tuberculosis reactivation. [U.S. Boxed Warnings]: Patients should be evaluated for latent tuberculosis infection with a tuberculin skin test prior to therapy. Treatment of latent tuberculosis should be initiated before use. Patients with initial negative tuberculin skin tests should receive continued monitoring for tuberculosis throughout treatment; active tuberculosis has developed in this population during treatment. Use with caution in patients who have resided in regions where tuberculosis is endemic

Drug interactions: Link: http://www.drugs.com/drug-interactions/adalimumab,humira.html

A total of 291 drugs (902 brand and generic names) are known to interact with Humira (adalimumab).

• 163 major drug interactions (510 brand and generic names)
• 114 moderate drug interactions (325 brand and generic names)
• 14 minor drug interactions (67 brand and generic names)

Show all medications in the database that may interact with Humira (adalimumab).

May interact with vaccines: BCG and live vaccines.  

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

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