adalimumab (Humira, Amjevita, adalimumab-atto)

Dosing and uses of Humira, Amjevita (adalimumab)

• Adult
• Pediatric

 

Adult dosage forms and strengths

prefilled syringe/pen

• 40mg/0.8mL (Humira, Amjevita)

Biosimilars to Humira

• Amjevita (adalimumab-atto)

 

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 SC q2wk

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 adalimuamb 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 SC q2wk

Dosing considerations

• 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

 

Ankylosing Spondylitis

Humira, Amjevita

Indicated for reduction of signs and symptoms of active ankylosing spondylitis

40 mg SC q2wk

Dosing considerations

• 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 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 SC once, then, after 1 week, 40 mg SC q2wk

 

Crohn 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 disease who have had inadequate response to conventional therapy; may be used in patients who have lost response to or are intolerant of infliximaB

Induction: 160 mg 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 q2wk

Dosing considerations

• Some patients may require weekly 40-mg dose for maintenance

 

Ulcerative Colitis

Humira, Amjevita

Indicated for treatment of ulcerative colitis unresponsive to immunosuppressants (eg, corticosteroids, azathioprine, 6-mercaptopurine [6-MP])

Induction: 160 mg 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 q2wk

Continue maintenance dose only if evidence of clinical remission is apparent by 8 weeks of therapy

 

Hidradenitis Suppurativa

Humira

Indicated for treatment of moderate-to-severe hidradenitis suppurativa (Hurley stage 2 and Hurley stage 3 disease)

Induction: 160 mg 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 qwk

 

Uveitis

Humira

Indicated for treatment of noninfectious intermediate, posterior, and panuveitis in adults

80 mg SC once, then, after 1 week, 40 mg SC q2wk

 

Behcet's Disease (Orphan)

Orphan designation for treatment of Behcet's disease

Sponsor

• Mucora; 32b Eisenberg St; Rehovot 7628810 Israel

 

Pediatric dosage forms and strengths

prefilled syringe/pen

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

Biosimilars to Humira

• Amjevita (adalimumab-atto)

 

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

• <2 years or <10 kg: Safety and efficacy not established
• ≥2 years
  • 10 kg to <15 kg: 10 mg SC q2wk
  • 15 kg to <30 kg: 20 mg SC q2wk
  • ≥30 kg: 40 mg SC q2wk

Amjevita

• <4 years: Safety and efficacy not established
• ≥4 years
  • 15 kg to <30 kg: 20 mg SC q2wk
  • ≥30 kg: 40 mg SC q2wk

 

Pediatric Crohn Disease

Humira

Indicated to reduce signs and symptoms, and achieve and maintain clinical remission in pediatric patients with moderately to severely active Crohn disease who have had an inadequate response to corticosteroids or immunomodulators (eg, azathioprine, 6-mercaptopurine, methotrexate)

<6 years: Safety and efficacy not established

≥6 years (17 kg to <40 kg)

• Induction: 80 mg 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 q2wk

≥6 years (>40 kg)

• Induction: 160 mg SC on Day 1 (administer as four 40 mg injections in one day or as two 40 mg injection 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 q2wk

 

Ulcerative Colitis (Orphan)

Orphan designation for pediatric ulcerative colitis

Orphan sponsor

• Abbott Laboratories; Global Pharmaceutical Research & Development; Abbott Park, IL 60064

 

Humira, Amjevita (adalimumab) adverse (side) effects

>10%

Injection site pain (12-20%)

Upper respiratory tract infection (URTI) (17%)

Increased creatine phosphokinase (15%)

Headache (12%)

Rash (12%)

Sinusitis (11%)

 

1-10%

Nausea (9%)

Urinary tract infection (UTI) (8%)

Abdominal pain (7%)

Flulike syndrome (7%)

Hyperlipidemia (7%)

Back pain (6%)

Hypercholesterolemia (6%)

Hematuria (5%)

Hypertension (5%)

Increased alkaline phosphatase (5%)

 

<1%

Allergic reactions

Hematologic disorder (leukopenia, thrombocytopenia, pancytopenia, aplastic anemia)

 

Postmarketing Reports

General disorders and administration site conditions: Pyrexia

Hepato-biliary disorders: Liver failure, hepatitis

Immune system disorders: Sarcoidosis

Neoplasms benign, malignant and unspecified (incl cysts and polyps): Merkel Cell Carcinoma (neuroendocrine carcinoma of the skin)

Nervous system disorders: Demyelinating disorders (eg, 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

 

Warnings

Black box warnings

Serious infection risk

• Increased risk for developing serious infections resulting in hospitalization or death; most patients were taking concomitant immunosuppressants (eg, methotrexate, corticosteroids)
• Patients older than 65 years may be at greater risk
• Discontinue if patient develops serious infection or sepsis
• Reported infections include the following:
• (1) Active TB, including reactivation of latent TB (frequently present with disseminated or extrapulmonary disease); test for latent TB before use and during therapy; treat latent infection before use
• (2) Invasive fungal infections (eg, 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 (eg, Legionella, Listeria), mycobacterial (eg, tuberculosis), and viral (eg, 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 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 lymphome (HSTCL) 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)

 

Contraindications

None listed on FDA-approved labeL

 

Cautions

Consider discontinuance if hematologic disorder occurs (thrombocytopenia, pancytopenia, leukopenia)

Coadministration with interleukin (IL)-1 blockers (eg, anakinra, ustekinumab) may lead to serious infections and neutropenia

Coadministration of TNF blockers with abatacept showed 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 Black box 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 Black box warnings)

Occurrence of leukemia and new-onset psoriasis reported in patients treated with TNF blockers (see Black box 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 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 vaccinating (live or live-attenuated) exposed infants

If possible, patients with JIA should be current with immunization guidelines prior to initiating adalimumab; may receive concurrent vaccinations (except for live vaccines) while taking adalimumaB

Autoimmunity may result in formation of autoantibodies and, rarely, development of lupuslike syndrome; if patient develops symptoms suggestive of lupus-like syndrome following treatment with adalimumab, discontinue treatment

Hypersensitivity reactions (eg, 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; TNFalpha inhibitors should only be considered in patients with HF if there are no other reasonable treatment options, and then consider only in patients with compensated HF

 

Pregnancy and lactation

Pregnancy category: B (pregnancy registry established; 1-877-311-8972)

IgG1 is actively transferred across the placenta during the third trimester of pregnancy

Lactation: 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

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Humira, Amjevita (adalimumab)

Mechanism of action

Recombinant human anti-TNF-α IgG1 monoclonal antibody; blocks inflammatory activity of TNF-α; specifically binds to TNF-α and blocks its interaction with p55 and p75 cell surface TNF receptors; also lyses surface TNF-expressing cells in vitro and modulates biologic responses responsible for leukocyte migration

 

Absorption

Bioavailability: 64%

Peak plasma time (40-mg dose): 131 ± 56 hr

Peak plasma concentration: 4.7 ± 1.6 mcg/mL

 

Distribution

Vd: 4.7-6 L

 

Elimination

Half-life: 10-20 days

Total body clearance: 12 mL/hr

 

Administration

Instructions

Instruct patients using the pen or prefilled syringe to inject the full amount in the syringe, according to the directions provided

Injections should occur at separate sites in the thigh or abdomen; rotate injection sites and do not give injections into areas where the skin is tender, bruised, red, or hard