Adalimumab

Name: Adalimumab

What other drugs will affect adalimumab?

Some drugs should not be used together with adalimumab. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with adalimumab, especially:

  • abatacept;

  • anakinra;

  • azathioprine, mercaptopurine; or

  • certolizumab, golimumab, infliximab, rituximab.

This list is not complete. Other drugs may interact with adalimumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Adalimumab Dosage and Administration

General

Concomitant Therapy

  • Methotrexate, other nonbiologic DMARDs, corticosteroids, NSAIAs, and/or analgesics may be continued in adults with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.1

  • Methotrexate, corticosteroids, NSAIAs, and/or analgesics may be continued in pediatric patients with juvenile idiopathic arthritis.1

  • Aminosalicylates and/or corticosteroids may be continued in adults with Crohn’s disease or ulcerative colitis.1 Azathioprine, mercaptopurine, or methotrexate may be continued, if necessary, in adults with Crohn’s disease.1 Azathioprine and mercaptopurine may be continued, if necessary, in adults with ulcerative colitis.1 (See Malignancies and Lymphoproliferative Disorders under Cautions.)

Administration

Sub-Q Injection

Available in prefilled syringes, prefilled injection pens, and vials; all are preservative free for single use only.1 Vials are for institutional use only; use promptly after withdrawing solution from vial.1

Administer by sub-Q injection every other week or every week.1

Administer sub-Q injections into thighs or abdomen; do not make abdominal injections within 5.18 cm (2 inches) of the umbilicus.36 37 Rotate injection sites.36 37 Give new injections ≥2.54 cm (1 inch) from an old site; do not make injections into areas where the skin is tender, bruised, red, or hard, or into scars or stretch marks.36 37 Do not inject into psoriatic lesions.36 37

Intended for use under the guidance and supervision of a clinician, but may be self-administered if the clinician determines that the patient and/or their caregiver is competent to safely administer the drug after appropriate training and with medical follow-up as necessary.1 The initial self-administered dose should be made under the supervision of a health-care professional.1

Dosage

Pediatric Patients

Juvenile Arthritis Sub-Q

Children 4–17 years of age weighing 15 to <30 kg: 20 mg once every other week.1

Children 4–17 years of age weighing ≥30 kg: 40 mg once every other week.1

Adults

Rheumatoid Arthritis Sub-Q

40 mg once every other week.1

Patients not receiving methotrexate may obtain additional benefit from once weekly doses of 40 mg.1

Psoriatic Arthritis Sub-Q

40 mg once every other week.1

Ankylosing Spondylitis Sub-Q

40 mg once every other week.1

Crohn’s Disease Sub-Q

160 mg once on day 1 (as four 40-mg injections in one day or as two 40-mg injections per day for 2 consecutive days), followed by 80 mg once 2 weeks later (on day 15).1 Start maintenance dosage of 40 mg once every other week on day 29 (2 weeks after the 80-mg dose).1

Ulcerative Colitis Sub-Q

160 mg on day 1 (as four 40-mg injections in one day or as two 40-mg injections per day for 2 consecutive days), followed by 80 mg once 2 weeks later (on day 15).1 Start maintenance dosage of 40 mg once every other week on day 29 (2 weeks after the 80-mg dose).1 If clinical remission is not achieved by 8 weeks (day 57), discontinue adalimumab.1

Plaque Psoriasis Sub-Q

Initially, 80 mg followed by 40 mg once every other week (maintenance dosage) starting 1 week after the initial dose.1

Prescribing Limits

Adults

Crohn’s Disease

Manufacturer states safety and efficacy of continuing adalimumab beyond 1 year have not been evaluated in clinical studies.1

Plaque Psoriasis

Manufacturer states safety and efficacy of continuing adalimumab beyond 1 year have not been evaluated in clinical studies.1

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Adalimumab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use

20 mg/0.4 mL

Humira (available as disposable prefilled syringes with alcohol swabs)

Abbott

40 mg/0.8 mL

Humira (available as disposable prefilled syringes and prefilled injection pens with alcohol swabs, and as single-use vials)

Abbott

Off Label Uses

Pyoderma gangrenosum

Preliminary data suggest that adalimumab could be successful as an adjunct therapy or monotherapy for the treatment of severe pyoderma gangrenosum. Adalimumab has been shown to be beneficial in refractory pyoderma gangrenosum in cases in which infliximab and etanercept have failed. Controlled studies are needed to evaluate the efficacy and safety of adalimumab in order to fully determine its place in the treatment of pyoderma gangrenosum.

Uveitis (children/adolescents)

Results from noncontrolled data show that adalimumab is effective in treating uveitis in children and adolescents. However, no prospective controlled clinical trials have been performed. Adalimumab has several safety concerns, including a black box warning regarding serious infections and lymphomas. Further data are needed to establish the efficacy, safety, optimal dosage, and length of adalimumab therapy in the treatment of uveitis in children. An expert review panel recommends adalimumab as a third-line treatment option in children with noninfectious uveitis.

Dosing Adult

Note: Amjevita (adalimumab-atto) is approved as a biosimilar agent to Humira. Approved uses may vary (consult product labeling).

Ankylosing spondylitis: SubQ: 40 mg every other week (may continue methotrexate, other nonbiologic DMARDS, corticosteroids, NSAIDs and/or analgesics)

Crohn disease: SubQ (may continue aminosalicylates and/or corticosteroids; if necessary, azathioprine, mercaptopurine, or methotrexate may also be continued):

Initial: 160 mg (given as four 40 mg injections on day 1 or given as two 40 mg injections per day 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).

Hidradenitis suppurativa (Humira only): SubQ:

Initial: 160 mg (given as four 40 mg injections on day 1 or given as two 40 mg injections per day over 2 consecutive days), then 80 mg 2 weeks later (day 15).

Maintenance: 40 mg every week beginning day 29.

Plaque psoriasis: SubQ:

Initial: 80 mg as a single dose

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

Psoriatic arthritis: SubQ: 40 mg every other week (may continue methotrexate, other nonbiologic DMARDS, corticosteroids, NSAIDs and/or analgesics)

Pyoderma gangrenosum (off-label use): SubQ: 40 to 80 mg every week or every other week (Fonder 2006; Heffernan 2007; Hubbard 2005; Jacob 2008). Additional data may be necessary to further define the role of adalimumab in the treatment of this condition.

Rheumatoid arthritis: SubQ: 40 mg every other week (may continue methotrexate, other nonbiologic DMARDS, corticosteroids, NSAIDs, and/or analgesics); patients not taking concomitant methotrexate may increase dose to 40 mg every week

Ulcerative colitis: SubQ (may continue aminosalicylates and/or corticosteroids; if necessary, azathioprine, or mercaptopurine may also be continued):

Initial: 160 mg (given as four 40 mg injections on day 1 or given as two 40 mg injections per day 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.

Uveitis (Humira only): SubQ:

Initial: 80 mg as a single dose

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

Dosing Pediatric

Note: Amjevita (adalimumab-atto) is approved as a biosimilar agent to Humira. Approved uses may vary (consult product labeling).

Crohn disease (Humira only): SubQ:

Children ≥6 years and Adolescents:

17 kg to <40 kg:

Initial: 80 mg (administered as two 40 mg injections on day 1), then 40 mg 2 weeks later (day 15).

Maintenance: 20 mg every other week beginning week 4 (day 29).

≥40 kg:

Initial: 160 mg (administered as four 40 mg injections on day 1 or as two 40 mg injections per day over 2 consecutive days), then 80 mg 2 weeks later (day 15; given as two 40 mg injections on the same day).

Maintenance: 40 mg every other week beginning week 4 (day 29).

Juvenile idiopathic arthritis (JIA): SubQ:

Children ≥2 years (Humira) or ≥4 years (Amjevita) and Adolescents:

May continue methotrexate, corticosteroids, NSAIDs and/or analgesics.

Humira (only): 10 to <15 kg: 10 mg every other week

Amjevita and Humira: 15 kg to <30 kg: 20 mg every other week

Amjevita and Humira: ≥30 kg: 40 mg every other week

BSA-based dosing (off-label):

2 to <4 years or ≥4 years and <15 kg: 24 mg/m2/dose (maximum: 20 mg/dose) every other week (Kingsbury 2014)

4 to 17 years: 24 mg/m2/dose (maximum: 40 mg/dose) every other week (Lovell 2008)

Uveitis (Humira only): Limited data available; dosing regimens variable; SubQ:

Body surface area-directed dosing: Children ≥4 years and Adolescents: 24 or 40 mg/m2 every 2 weeks; maximum dose 40 mg/dose (Gallagher 2007; Simonini 2011). Dosing based on one prospective trial comparing 24 mg/m2/dose every 2 weeks of adalimumab (n=16, ages 6 to 12 years) to infliximab (n=17, ages 5 to 13 years) and on a retrospective trial of biologic response modifiers, including five patients who received adalimumab at 40 mg/m2/dose every 2 weeks.

Weight-directed dosing: Children ≥2 years and Adolescents (Biester 2007; Sens 2012; Tynjala 2008):

<30 kg: 20 mg every other week

>30 kg: 40 mg every other week

Drug Interactions

Abatacept: Anti-TNF Agents may enhance the adverse/toxic effect of Abatacept. An increased risk of serious infection during concomitant use has been reported. Avoid combination

Anakinra: Anti-TNF Agents may enhance the adverse/toxic effect of Anakinra. An increased risk of serious infection during concomitant use has been reported. Avoid combination

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Avoid combination

Canakinumab: Anti-TNF Agents may enhance the adverse/toxic effect of Canakinumab. Specifically, the risk for serious infections and/or neutropenia may be increased. Avoid combination

Certolizumab Pegol: Anti-TNF Agents may enhance the immunosuppressive effect of Certolizumab Pegol. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

CycloSPORINE (Systemic): Adalimumab may decrease the serum concentration of CycloSPORINE (Systemic). Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

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

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

InFLIXimab: Adalimumab may enhance the immunosuppressive effect of InFLIXimab. Avoid combination

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Rilonacept: Anti-TNF Agents may enhance the adverse/toxic effect of Rilonacept. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Theophylline Derivatives: Adalimumab may decrease the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy

Tocilizumab: May enhance the immunosuppressive effect of Anti-TNF Agents. Avoid combination

Tofacitinib: Anti-TNF Agents may enhance the adverse/toxic effect of Tofacitinib. Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Vedolizumab: Anti-TNF Agents may enhance the adverse/toxic effect of Vedolizumab. Avoid combination

Warfarin: Adalimumab may decrease the serum concentration of Warfarin. Monitor therapy

Usual Adult Dose for Ankylosing Spondylitis

40 mg subcutaneously every other week

Comments:
-In the treatment of rheumatoid arthritis, some patients not taking concomitant methotrexate may derive additional benefit from increasing the dosing frequency to 40 mg every week.
-Methotrexate, glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs, analgesics, or other disease modifying agents may be given concomitantly.

Uses:
-To reduce signs and symptoms in adult patients with active ankylosing spondylitis (AS)
-Alone or in combination with non-biologic DMARDs to inhibit the progression of structural damage and improve physical function in adult patients with active psoriatic arthritis
-Alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs) to reduce signs and symptoms, inducing major clinical response, inhibit the progression of structural damage, and improve physical function in adult patients with moderately to severely active rheumatoid arthritis (RA)

Usual Adult Dose for Rheumatoid Arthritis

40 mg subcutaneously every other week

Comments:
-In the treatment of rheumatoid arthritis, some patients not taking concomitant methotrexate may derive additional benefit from increasing the dosing frequency to 40 mg every week.
-Methotrexate, glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs, analgesics, or other disease modifying agents may be given concomitantly.

Uses:
-To reduce signs and symptoms in adult patients with active ankylosing spondylitis (AS)
-Alone or in combination with non-biologic DMARDs to inhibit the progression of structural damage and improve physical function in adult patients with active psoriatic arthritis
-Alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs) to reduce signs and symptoms, inducing major clinical response, inhibit the progression of structural damage, and improve physical function in adult patients with moderately to severely active rheumatoid arthritis (RA)

Usual Adult Dose for Ulcerative Colitis

-Initial dose: 160 mg subcutaneously on Day 1 (given in one day or split over 2 consecutive days), followed by 80 mg subcutaneously 2 weeks later (Day 15)
-Maintenance dose (beginning 2 weeks later [Day 29]): 40 mg subcutaneously every other week

Comments:
-Aminosalicylates and/or corticosteroids may be continued during treatment.
-Azathioprine, 6-mercaptopurine (6-MP), or methotrexate (MTX) may be continued during treatment if necessary.
-Treatment beyond one year in Crohn's Disease has not been established.
-Treatment in ulcerative colitis should only be continued in patients who have shown evidence of clinical remission by eight weeks (Day 57) of therapy.

Uses:
-To reduce signs and induce and maintain remission in adult patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy; to reduce signs and induce remission in these patients if they have also lost response to or are intolerant to infliximab
-To induce and maintain remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants such as corticosteroids, azathioprine, or 6-mercaptopurine (6-MP) (the effectiveness of this drug in patients who have lost response to or were intolerant to TNF blockers has not been established)

Usual Pediatric Dose for Juvenile Idiopathic Arthritis

2 years and older:
-For 10 kg (22 pounds) to less than 15 kg (33 pounds):10 mg subcutaneously every other week
-For 15 kg (33 pounds) to less than 30 kg (66 pounds): 20 mg subcutaneously every other week
-For 30 kg (66 pounds) or greater: 40 mg subcutaneously every other week

Comments:
-Safety and efficacy has not been established in patients with polyarticular JIA less than 2 years of age or in patients with a weight below 10 kg.
-Methotrexate, glucocorticoids, salicylates, NSAIDs, or analgesics may be continued during treatment.

Uses: To reduce symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) in pediatric patients 2 years of age and older, used alone or in combination with methotrexate

Usual Pediatric Dose for Crohn's Disease - Acute

6 years and older:
-For 17 kg (37 pounds) to less than 40 kg (88 pounds):
Initial dose: 80 mg subcutaneously (Day 1), then 40 mg subcutaneously 2 weeks later (Day 15)
Maintenance dose: 20 mg subcutaneously every other week
-For 40 kg (88 pounds) or greater:
Initial dose: 160 mg subcutaneously (Day 1) given in one day or split over 2 consecutive days, then 80 mg subcutaneously 2 weeks later (Day 15)
Maintenance dose: 40 mg subcutaneously every other week

Uses: To reduce symptoms and induce and maintain clinical remission in pediatric patients 6 years of age and older with moderately to severely active Crohn's disease who have had an inadequate response to corticosteroids or immunomodulators such as azathioprine, 6-mercaptopurine, or methotrexate

Dialysis

Data not available

Other Comments

Administration advice:
-Following adequate training in subcutaneous injection technique, patients may self-inject this drug.
-Self-injection sites include the thigh or abdomen.
-Injection sites should be rotated and adalimumab should not be injected into areas where the skin is tender, bruised, red, or hard.

Storage requirements:
-This drug should be refrigerated at 2 C to 8 C and kept from freezing.
-If necessary, single prefilled syringes or pens may be stored at room temperature (below 25 C) and protected from light for up to 14 days.
-Once removed from the refrigerator for storage at room temperature, the syringe must be used within 14 days or discarded, regardless of whether it is returned to the refrigerator or not.

General:
-There is an increased risk of lymphoma in rheumatoid arthritis patients with long standing, highly active, inflammatory disease.
-Use of live vaccines should be avoided during therapy.

Monitoring:
Cardiovascular: Signs of new or worsening congestive heart failure
Hematologic: Blood dyscrasias
Immunologic: Infections and development of autoantibodies
Neurologic: New onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease
Oncologic:
-Lymphomas or other malignancies, particularly in rheumatoid arthritis patients, patients with a history of malignancy, COPD patients, and patients with a history of heavy smoking
-Patients with a medical history of extensive immunosuppressant therapy and psoriasis patients with a history of PUVA treatment should be examined for the presence of nonmelanoma skin cancer prior to and during treatment.

Patient advice:
-Patients using a prefilled pen or syringe should inject the full amount in the device.
-If removing the syringe from the refrigerator for room temperature storage, record the date of removal to allow the syringe to be discarded after the maximum of 14 days if not used.

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